会议简要日程 日期上午下午晚上 月 7 日报到 (2:30 20:00), 南大国际会议中心一楼大堂 月 8 日 开幕式及大会报告一楼紫金厅 分会报告二楼各会议厅 墙报一楼 紫金厅门口 月 9 日 分会报告二楼各会议厅 分会报告二楼各会议厅 月 20 日 分会报告 二楼各会议厅 颁奖典礼 获奖人报告

中国化学会 第 4 届全国计算 ( 机 ) 化学学术会议 暨分子模拟国际论坛 The 4 th National Computer Chemistry Conference of China & International Workshop on Molecular Simulations 会议手册 中国化学会计算机化学专业委员会南京大学化学化工学院 207..7-20 南京

会议简要日程 日期上午下午晚上 月 7 日报到 (2:30 20:00), 南大国际会议中心一楼大堂 月 8 日 开幕式及大会报告一楼紫金厅 分会报告二楼各会议厅 墙报一楼 紫金厅门口 月 9 日 分会报告二楼各会议厅 分会报告二楼各会议厅 月 20 日 分会报告 二楼各会议厅 颁奖典礼 获奖人报告及闭幕式 一楼紫金厅 注 : 分会一洁行厅, 二以行厅, 三金陵厅, 四躬学厅, 五中大厅 Zhongda Hall

目录 会议概况 参会须知 3 开 闭幕式及大会报告. 5 第一分会 6 第二分会 0 第三分会 3 第四分会 6 第五分会 20 墙报展示 22

中国化学会第 4 届全国计算 ( 机 ) 化学学术会议 由中国化学会主办, 中国化学会计算机化学专业委员会和南京大学化学化工学院承办, 南京大学理论与计算化学研究所 配位化学国家重点实验室 生命分析国家重点实验室 高性能高分子材料教育部重点实验室和江苏省化学化工学会协办的第十四届全国计算 ( 机 ) 化学学术会议将于 207 年 月 7 日至 20 日在江苏省南京市南京大学仙林校区国际会议中心举行 此次会议将全面展示近年来我国在计算 ( 机 ) 化学领域取得的最新进展及成果, 深入探讨所面临的机遇 挑战及未来发展方向, 致力于促进学术界与产业界的沟通联系, 推进我国计算机化学的健康发展 会议将分为开 闭幕式和大会报告及以下五个并行的分会场, 共组织 9 场大会报告 24 场邀请报告 57 场口头报告和 34 张墙展报告 会议邀请函和详细摘要请在会议网站自行下载, 下载网址 http://itcc.nju.edu.cn/nsccc207/. 化学信息学与药物设计 ( 二楼洁行厅, 主席罗海彬 ); 2. 化学计量学与生命化学计算 ( 二楼以行厅, 主席陈增萍 ); 3. 化工与材料模拟计算 ( 二楼金陵厅, 主席汪蓉和吕玲红 ); 4. 化学理论计算与分子模拟 ( 二楼躬学厅, 主席李有勇和马海波 ); 5. 分子模拟国际论坛 ( 二楼中大厅, 主席胡文兵 ) 2

学术委员会 主任 : 蒋华良 委员 : 陈维明陈增萍邓光辉杜一平丁晓琴侯廷军胡文兵郭洪霞纪志梁蒋华良金钟来鲁华李浩然李洪林李华李梦龙李松李通化李晓霞李有勇刘轶陆文聪卢小泉罗海彬罗小民裴剑锋乔圆圆邵学广石乐明盛春泉孙素琴孙淮唐赟万坚王任小温浩吴海龙徐筱杰徐峻杨明君杨胜勇姚建华姚小军袁洪福张健张卓勇郑清川周涵 朱 峰朱群雄朱维良朱玉山邹小勇 组织委员会 主席 : 蒋华良黎书华总负责 : 胡文兵成员 : 夏兴华左景林鞠熀先李育佳束羽汪蓉马海波 陈葳陈瑶李伟罗海彬陈增萍吕玲红李有勇 3

参会须知 报告人须知第 4 届全国计算 ( 机 ) 化学学术会议组委会诚挚地欢迎您于金秋季节前来南京参会, 并感谢您为大会带来精彩的报告! 为了您的方便和会议的顺利进行, 敬请您留意以下几点 :. 报告文件请保存为 PPT 格式, 同时建议将 PPT 格式转化成 PDF 文件以备用 2. 组委会为各会场统一提供预装 Windows 系统的电脑, 报告人无需自带电脑 报告结束后统一删除所有 PPT 3. 请在会议开始前 5 分钟将 PPT 拷入相应分会提供的电脑中 4. 大会报告的时间为 :40 分钟演讲 ( 不设提问环节 ) 邀请报告的时间为 :5 分钟演讲 +5 分钟提问口头报告的时间为 :2 分钟演讲 +3 分钟提问 5. 会议墙报展于 月 8 日晚 9:00-2:00 展出, 地点在国际会议中心一楼紫金厅门口展区 请 8 日下午茶歇和晚餐期间自行张贴墙报至指定编号位置 墙报统一规格.2m 高 0.9m 宽, 会场提供胶带等粘贴工具 会场提示为了不打扰其他参会代表听报告, 同时更好地尊重知识产权, 除工作人员为大会宣传进行必要的拍摄之外, 我们不建议代表在听报告或看墙展时擅自拍照或录像 在会场时, 手机也请调到振动档 会场提供酒店免费 Wi-Fi, 用户名 ndgjhyzx, 密码 89686666, 其中二楼中大厅只能通过 NJU-WLAN 连接查看校园网及会议网站 用餐提醒早餐由各个酒店自行安排, 月 7 日晚至 20 日晚的午餐和晚餐凭票用餐, 就餐地点 : 南京大学国际会议中心一楼 7 日白天早到的代表请在各酒店 大学餐厅或地铁站附近自行用午餐 班车服务 月 7 日下午 点整国际会议中心 - 栖霞山公园下午 2 点整国际会议中心 - 栖霞山公园下午 4 点整栖霞山公园 - 国际会议中心下午 5 点整栖霞山公园 - 国际会议中心下午 5 点整中公汇悦酒店 - 国际会议中心下午 6 点整国际会议中心 - 中公汇悦酒店 月 7 日下午 点到 8 点有小巴循环往返于中公汇悦酒店 - 国际会议中心 - 仙林招待所 月 8 日上午 8:0 中公汇悦酒店 - 国际会议中心 8:20 仙林招待所 - 国际会议中心 8:30 中公汇悦酒店 - 国际会议中心 4

下午 20:30 和 2:05 国际会议中心 - 中公汇悦酒店 2:5 国际会议中心 - 仙林招待所 月 9 日上午 8:20 中公汇悦酒店 - 国际会议中心 8:30 仙林招待所 - 国际会议中心 8:40 中公汇悦酒店 - 国际会议中心下午 9 点整和 20 点整国际会议中心 - 中公汇悦酒店 9:5 国际会议中心 - 仙林招待所 月 20 日上午 8:20 中公汇悦酒店 - 国际会议中心 8:30 仙林招待所 - 国际会议中心 8:40 中公汇悦酒店 - 国际会议中心下午 9 点整和 20 点整国际会议中心 - 中公汇悦酒店 9:5 国际会议中心 - 仙林招待所 月 2 日上午 9 点到 2 点有小巴循环往返于中公汇悦酒店 - 南大仙林地铁站 - 仙林招待所 会务信息 如您在会议期间有任何问题, 欢迎您与大会会务组相关负责人联系 总负责 胡文兵 364585262 住宿相关 李伟 820547575 注册报到相关已缴费组 :( 签到, 领会议资料, 签字领发票 ) 汪蓉 384052398 未缴费组 :( 注册签到, 缴费, 领会议资料 ) 陈葳 893909078 墙报技术服务徐承欢 5950572098 会场技术服务马海波 894788480 交通及导引 王季平 36003965 会务组地点 南京大学国际会议中心大堂及二楼 医疗保障服务 8968520 校保卫处电话 896850 5

开 闭幕式及大会报告 ( 一楼紫金厅 Zijin Hall) 日期时间报告人题目 8:50-9:20 国际会议中心门口西侧台阶合影, 紫金厅开幕式 9:20-0:00 陈洪渊 PL0 ( 南京大学 ) 生命化学前沿及发展机遇 207..8 0:00-0:40 杨玉良 My view on the biological PL02 ( 复旦大学 ) importance of charged systems 0:40-:20 蒋华良 ( 中国科学院上理论计算驱动的药物研究 PL03 海药物研究所 ) :20-2:00 PL04 吴国胜 ( 康龙化成 ( 北 京 ) 新药公司 ) 基于结构的药物设计 : 挑战和机会 3:30-3:50 计算机化学奖和研究生优秀墙报奖颁奖仪式 3:50-4:30 俞汝勤 化学计量学助推分析化学研究 PL05 ( 湖南大学 ) 范式转换 4:30-5:0 徐筱杰 PL06 ( 北京大学 ) 计算化学在中药研究中的应用 207..20 5:0-5:50 来鲁华 从基于结构到基于系统的药物 PL07 ( 北京大学 ) 设计 5:50-6:30 PL08 王任小 ( 中国科学院上海有机化学研究所 ) Forging the basis of developing protein-ligand interaction scoring functions 6:30-7:0 侯廷军 基于靶点结构的虚拟筛选中个 PL09 ( 浙江大学 ) 性化策略的探讨 7:0-7:30 闭幕式 6

第一分会化学信息学与药物设计 ( 二楼洁行厅 Jixing Hall) 207 年 月 8 日下午 主持人 : 罗海彬 朱维良 时间 报告人 单位 题目 3:30-3:50 I--0 来鲁华 北京大学 基于系统生物学的中药机理研究 3:50-4:0 I--02 侯廷军 浙江大学 新型 ALK 抑制剂的设计和优化 4:0-4:30 李建新基于 Tph- 的抗骨质疏松分子的设南京大学 I--03 计, 合成与活性 4:30-4:50 付伟复旦大学 Computational design aminergic I--04 GPCR agonists/antagonists A systematic review of reverse 4:50-5:0 黄遵楠广东医科大学 screening methods in search for I--05 protein targets of chemopreventive compounds 5:0-5:30 I--06 陈彦涛 深圳大学 5:30-6:00 茶歇 Supramolecular interaction between insulin and Cp- peptide and their assembly as rapid-acting formulation 6:40-7:00 I--09 7:00-7:20 I--0 7:20-7:35 O--0 万坚 李加忠 徐志建 华中师范大学 兰州大学 中国科学院上海药物研究所 主持人 : 来鲁华 侯廷军 时间 报告人 单位 题目 6:00-6:20 中国科学院上海药朱维良 New efficient methods for sampling I--07 物研究所 protein conformation 6:20-6:40 中国科学院上海有关于化学信息学应用与发展的若干姚建华 I--08 机化学研究所思考 Multiple-levels potential-energysurfaces crossing (MSC) strategy for accurate prediction of the complex molecular conformations with lowerenergy-states 抗雄激素类前列腺癌治疗药物耐药机制的理论研究及新型雄激素受体拮抗剂的筛选 PDB 数据库中被低估的卤键 7

207 年 月 9 日上午 主持人 : 徐峻 唐贇时间报告人单位题目 On the Theory of Comparing Two 9:00-9:20 王任小中国科学院上海有机 Models with Correlation I-- 化学研究所 Coefficients Veratramine modulates 9:20-9:40 李洪林华东理工大学 AP--dependent gene transcription I--2 by directly binding to programmable DNA 9:40-0:00 中国科学院上海药物数据驱动的药物设计方法学及应郑明月 I--3 研究所用研究 2D/3D-QSAR 方法相结合筛选 0:00-0:5 李书艳兰州大学与 O--02 发现具有新型骨架结构的 CDPK 抑制剂 0:5-0:35 茶歇 主持人 : 王任小 李洪林 时间 报告人 单位 题目 0:35-0:55 高性能计算支持下的药物分子设徐峻中山大学 I--4 计学 : 进展与展望 0:55-:5 I--5 唐贇 华东理工大学 药物安全性的计算机预测研究 :5-:30 计算机辅助多靶点抗抑郁药物作薛伟伟重庆大学 O--03 用机制研究 :30-:45 O--04 龚正 上海交通大学 207 年 月 9 日下午 8 A simple approach to enhance the temperature transferability of all-atom force field 主持人 : 张健 许永时间报告人单位题目 3:30-3:50 新型抗肺动脉高压 PDE5 抑制罗海彬中山大学 I--6 剂的设计与优化 ADReCS-Target: target profiles for 3:50-4:0 纪志梁厦门大学 aiding drug safety research and I--7 application Identification of next generation 4:0-4:30 朱峰浙江大学 innovative therapeutic target from I--8 OMICs data to facilitate the cutting edge research of precision medicine 4:30-4:50 I--9 翟红林 兰州大学 蛋白质磷酸化位点预测新方法研究

4:50-5:0 I--20 5:0-5:25 O--05 陈超 曹东升 广东药科大学 中南大学 5:25-5:45 茶歇 Improving the design of non-interaction pairs in supervised prediction of drug-target interactions 基于系统药理学的药物副作用预 测与药物作用机制研究 主持人 : 纪志梁 朱峰时间报告人单位题目 5:45-6:05 张健上海交通大学 Identification and validation of I--2 novel kinase allosteric sites 6:05-6:25 中国科学院广州生物许永 New strategy for prostate cancer I--22 医药与健康研究院 Knowledge-based pose filter 6:25-6:40 中国医学科学院药物夏杰 ensemble as etructure-based virtual O--06 研究所 screening tools to facilitate the discovery of FXR agonists 6:40-6:55 O--07 6:55-7:0 O--8 7:0-7:25 O--9 7:25-7:40 O--0 周玥 李占潮 李佳 饶立 主持人 : 裴剑锋 钟世钧 北京工业大学 广东药科大学 中国科学院上海有机化学研究所 华中师范大学 207 年 月 20 日上午 基于药效片段组合的新型蛋白激酶 CK2 抑制剂设计 Predicting binding affinity of compound-protein interactions on a proteome scale by random forest using network topology features 聚合物光电材料 P(BDTn-DTBT) 和 P(BDTn-fDTBT) 分子与材料性质的理论计算 Nonfitting protein-ligand interaction scoring function based on DFT 时间报告人单位题目 9:00-9:20 I--23 阳怀宇 华东师范大学 K2P 设计 通道动态构象多位点药物 9:20-9:40 上海鹰谷信息科技有以信息化和人工智能建立基于化邓光辉 I--24 限公司学结构的大数据 9

9:40-9:55 O-- 段谟杰 中国科学院武汉物理与数学研究所 The allosteric effects on protein induced by small ligands studied by molecular dynamics simulations 9:55-0:0 O--2 黄迎 中国科学院上海有机化学研究所 危险化学品信息查询系统的建立与应用 0:0-0:35 茶歇 主持人 : 阳怀宇 邓光辉 时间报告人单位题目 0:35-0:55 I--25 裴剑锋 北京大学 Prediction of protein protein interaction using a deep-learning algorithm 0:55-:5 I--26 钟世钧 大连理工大学 呈现蛋白质构象转变的插值旋转优化方法 :5-:30 O--3 董界 中南大学湘雅药学院 TargetNet: 多靶点 QSAR 预测潜在的药物 - 靶点相互作用的在线计算平台 :30-:45 O--4 张庆上海大学材料机器学习平台 0

第二分会化学计量学与生命化学计算 ( 二楼以行厅 Yixing Hall) 207 年 月 8 日下午 主持人 : 陆文聪 阎爱侠 时间 报告人 单位 题目 3:30-3:50 高维化学计量学方法用于温控近红外邵学广南开大学 I-2-0 光谱数据分析 3:50-4:0 采样误差分布分析 (SEPA) 及其在近杜一平华东理工大学 I-2-02 红外光谱分析中的应用 4:0-4:30 I-2-03 4:30-4:45 O-2-0 4:45-5:00 O-2-02 5:00-5:5 O-2-03 5:5-5:30 O-2-04 陈达 第五鹏瑶 马丽 刘金金 崔晓宇 天津大学 天津工业大学 南开大学 兰州大学 南开大学 5:30-5:50 茶歇 The application of data driven Raman Spectroscopy in oil and gas exploration industry 一种用于复杂样品光谱信号的选择性集成预处理方法研究利用温控近红外光谱研究水在蛋白质水凝胶形成过程中的作用基于近红外光谱的温度效应同时定量分析混合物中的三种成分三维温控近红外光谱数据的多级成分分析 主持人 : 邵学广 杜一平 时间 报告人 单位 题目 5:50-6:0 I-2-04 陆文聪 上海大学 数据挖掘辅助材料设计研究进展 6:0-6:30 基于多领域数据信息融合的化合物致阎爱侠北京化工大学 I-2-05 癌性预测 6:30-6:45 水分子跨越纳米通道及生物膜的输运苏加叶南京理工大学 O-2-05 性质 6:45-7:00 上海科技大学周庆同核酸适配体的计算机模拟研究 O-2-06 ihuman 研究所 7:00-7:5 O-2-07 7:5-7:30 O-2-08 吴量 程平 上海交通大学 国家纳米科学中心 Cholesteric ordering in coarse-grained polymeric molecule with helical interaction Chiral self-assembly of phenylalanine molecules on Au()

207 年 月 9 日上午 主持人 : 倪永年 蒲雪梅 时间 报告人 单位 题目 9:00-9:20 西安石油大学 / 西激光诱导击穿光谱中的化学计量学理李华 I-2-06 北大学论与方法研究 9:20-9:40 甘峰中山大学 Mathematization of quantitative I-2-07 analysis Ensemble strategies and methods for 9:40-9:55 卞希慧天津工业大学 the spectral quantitative analysis of O-2-09 complex samples 中国热带农业科 9:55-0:0 云永欢基于集群分析的化学建模相关算法研学院环境与植物 O-2-0 究保护研究所 0:0-0:30 茶歇 主持人 : 李华 甘峰时间报告人单位题目 0:30-0:50 化学计量学在食品质量控制和食品安倪永年南昌大学 I-2-08 全机理研究中的应用 0:50-:0 网络方法在肿瘤基因分析和靶标蛋白蒲雪梅四川大学 I-2-09 研究中的应用 :0-:25 多元校正方法在临床复杂样本定性与文志宁四川大学 O-2- 定量分析中的应用 :25-:40 一类偏最小二乘法 : 算法 工具包与应徐路铜仁学院 O-2-2 用 :40-:55 基于化学计量学的两种总植物碱测定李跑湖南农业大学 O-2-3 方法的一致性研究 207 年 月 9 日下午 主持人 : 袁洪福 赵一雷 时间 报告人 单位 题目 3:30-3:50 机器学习在化学与生物学中的应用漫李梦龙四川大学 I-2-0 谈 3:50-4:0 基于深度学习的蛋白质相互作用预测邹小勇中山大学 I-2- 方法 4:0-4:30 酶分子催化机制 : 预反应态决定底物赵一雷上海交通大学 I-2-2 选择性? 4:30-4:50 I-2-3 高军 华中农业大学 蛋白核酸相互作用的理论模拟 4:50-5:05 振动光谱探针用于多肽构象态特征研蔡开聪福建师范大学 O-2-4 究 2

5:05-5:20 O-2-5 5:20-5:35 O-2-6 王舒瑜 程丹 南开大学 南开大学 5:35-6:00 茶歇 银镜基质用于近红外漫反射光谱定量血清中总胆红素的研究基于温控近红外光谱和独立成分分析研究寡肽的水合作用 主持人 : 李梦龙 邹小勇 时间 报告人 单位 题目 6:00-6:20 化学计量学在现代光谱过程分析袁洪福北京化工大学 I-2-4 技 6:20-6:40 术中的应用研究付海燕中南民族大学多元谱学新方法在食药质控中应用 I-2-5 6:40-6:55 中国科学院过程利用大规模 ReaxFF MD 初步探索孔郑默 O-2-7 工程研究所道对煤热解过程的影响 6:55-7:0 北京并行科技有并行科技, 助力高效提升化学计算应李伯杨 O-2-8 限公司用在超算上的性能 207 年 月 20 日上午 主持人 : 吴海龙 陈增萍 时间 报告人 单位 题目 9:00-9:20 I-2-6 张卓勇 首都师范大学 化学计量学与慢性肾病患者诊断 9:20-9:40 卢红梅中南大学 Application of chemometrics in I-2-7 untargeted metabolomics 9:40-9:55 基于代谢组学数据特征的稳健的易伦朝昆明理工大学 O-2-9 变 9:55-0:0 量选择方法研究张志敏中南大学 Fast pure ion chromatograms extraction O-2-20 method for LC-MS 0:0-0:35 茶歇 主持人 : 张卓勇 卢红梅 时间 报告人 单位 题目 0:35-0:55 复杂体系数学分离及精准定量研究进吴海龙湖南大学 I-2-8 展 0:55-:5 光谱形变定量分析理论及其应用研究陈增萍湖南大学 I-2-9 进展 :5-:30 多元曲线分辨旋转模糊评估和应对策张欣首都师范大学 O-2-2 略 基于遗传算法优化的约束背景双线性 :30-:45 张雅雄山西师范大学分解算法用于改进高效液相色谱灰色 O-2-22 分析体系的校正结果 3

第三分会化工与材料模拟计算 ( 二楼金陵厅 Jinling Hall) 207 年 月 8 日下午 主持人 : 邱枫 王建国 时间 报告人 单位 题目 3:30-3:50 史安昌 McMaster Periodic and aperiodic order in soft I-3-0 University matter systems 3:50-4:0 中国科学院长春孙昭艳 I-3-02 应用化学研究所 过冷液体结构与动力学的计算机模拟 4:0-4:30 刚 - 柔嵌段高分子的自组装结构及唐萍复旦大学 I-3-03 相 4:30-4:50 I-3-04 4:50-5:0 I-3-05 5:0-5:30 I-3-06 童朝晖 苗兵 宁波大学 变路径 Molecular dynamics simulation of the response of bi-disperse polyelectrolyte brushes to external electric fields 中国科学院大学聚电解质溶液相分离理论 张良顺华东理工大学共聚物引导自组装的动力学调控 5:30-5:50 茶歇 主持人 : 史安昌 孙昭艳 时间 报告人 单位 题目 5:50-6:0 王建国浙江工业大学 Experimental and theoretical study on I-3-07 supported nanocatalysts 6:0-6:30 李卫华复旦大学 SCFT study on the self-assembly of I-3-08 block copolymers 6:30-6:50 I-3-09 胡晶磊 南京大学 脂筏促进细胞粘附蛋白的键合 6:50-7:0 中国科学院长春稳态剪切下高分子的构象 动力学及陈继忠 I-3-0 应用化学研究所流变性质 7:0-7:25 纳米粒子单接枝高分子链体系的杨颖梓复旦大学 O-3-0 分 7:25-7:40 相行为徐玉赐宁波大学聚合物共混理论 : 单链构象及 θ 点 O-3-02 207 年 月 9 日上午 主持人 : 严大东 石彤非 时间 报告人 单位 题目 9:00-9:20 I-3- 吕玲红 南京工业大学 固载离子液体吸收 CO 2 9:20-9:40 胡兴邦 南京大学 高效 O 2 CO 2 活化催化剂设计 合 4

I-3-2 9:40-0:00 I-3-3 0:00-0:5 O-3-03 成及应用北京航空航天大通过调节蒸发速率实现分层胶体周嘉嘉学薄膜的制备马世营泰山学院嵌段共聚物诱导纳米粒子组装 0:5-0:35 茶歇 主持人 : 吕玲红 周嘉嘉 时间 报告人 单位 题目 0:35-0:55 I-3-4 严大东 北京师范大学 高分子结晶的局域跃迁模型 0:55-:5 中国科学院长春石彤非 I-3-5 应用化学研究所 :5-:35 北京航空航天大满兴坤 I-3-6 学 The drying of liquid droplets :35-:55 I-3-7 何学浩 天津大学 207 年 月 9 日下午 Polymer escape from confining nanotube in reverse flow 溶液中粒子聚集自组装热力学模拟研究 主持人 : 张兴华 钱虎军 时间 报告人 单位 题目 3:30-3:50 纳米粒子在细胞膜上的扩散动力学 : 燕立唐清华大学 I-3-8 分子模拟及理论分析 3:50-4:0 I-3-9 杨恺 苏州大学 多肽与细胞界面相互作用机制研究 4:0-4:30 中国科学院长春两性离子聚电解质毛刷表面自清朱有亮 I-3-20 应用化学研究所洁 4:30-4:50 机理的模拟研究罗孟波浙江大学高分子表面吸附的模拟研究 I-3-2 4:50-5:0 中国科学院长春张然 Role of salt and water in PSS/PDAC I-3-22 应用化学研究所 polyelectrolyte complex plasticization Polymer crystallization induced by 5:0-5:30 聂仪晶江苏大学 nanoparticles with different I-3-23 dimensions 5:30-5:50 茶歇 主持人 : 燕立唐 杨恺 时间 报告人 单位 题目 5:50-6:0 偶氮高分子体系响应性质的理论张兴华北京交通大学 I-3-24 研 6:0-6:30 究高分子 / 纳米粒子复合材料动力学性钱虎军吉林大学 I-3-25 质的计算机模拟 6:30-6:50 李剑锋 复旦大学 碳材料相关的理论模拟研究 5

I-3-26 6:50-7:0 I-3-27 7:0-7:30 I-3-28 7:30-7:45 O-3-04 朱雨田 周燕子 徐晓雷 中国科学院长春应用化学研究所 南京大学 中国科学院长春应用化学研究所 207 年 月 20 日上午 嵌段共聚物三维软受限自组装的实验与模拟研究非活性残基对酶催化反应能力的影响半刚性高分子体系粘度行为 主持人 : 蒋滢 尹玉华时间报告人单位题目 9:00-9:20 带电高分子刷性质及其应用的理杨爽北京大学 I-3-29 论研究 Insights into the endosomal escape 9:20-9:40 田文得苏州大学 mechanism via investigation of I-3-30 dendrimer membrane interactions 9:40-0:00 中国科学院长春基于软补丁粒子体系的超胶体结李占伟 I-3-3 应用化学研究所构设计与调 Theoretical investigation of the 0:00-0:5 白福全吉林大学 mechanism of photochemical ligand O-3-05 ejection in transition metal complex 0:5-0:35 茶歇 主持人 : 杨爽 田文得 时间 报告人 单位 题目 0:35-0:55 北京航空航天大蒋滢 I-3-32 学 短链聚合物体系相行为的理论研究 0:55-:5 链的拓扑结构对嵌段共聚物自组尹玉华南开大学 I-3-33 装 :5-:30 O-3-06 :30-:45 O-3-07 高洋洋 李亮 北京化工大学 上海交通大学 行为的影响分子动力学模拟与模型结合研究填料 ( 石墨烯, 碳纳米管 ) 接枝分子链对尼龙纳米复合材料导热性能的影 Molecular conformation study of gellan polysaccharide in crystal solution states and 6

第四分会化学理论计算与分子模拟 ( 二楼躬学厅 Gongxue Hall) 207 年 月 8 日下午 主持人 : 谢代前 李宝会时间报告人单位题目 3:30-3:50 I-4-0 3:50-4:0 I-4-02 4:0-4:30 I-4-03 4:30-4:50 I-4-04 4:50-5:0 I-4-05 5:0-5:30 I-4-06 周震 邓伟侨 林嘉平 蔡文生 董昊 柯卓锋 南开大学 中国科学院大连化学物理研究所 华东理工大学 南开大学 南京大学 中山大学 5:30-6:00 茶歇 Computational simulation and molecular design of organic electrode materials for Li ion batteries 精确范德华分子力场及其应用 Striped patterns self-assembled from rod-coil diblock copolymers on spherical substrates 基于自适应偏置力的自由能计算方法 Molecular-level computer simulations on the self-assembled peptides with catalytic activity 禀异 双功能体系催化储氢释氢 : 仿生策略的青出于蓝 主持人 : 周震 邓伟侨时间报告人单位题目 6:00-6:20 中国科学技术大表面单分子体系中的量子态的理论郑晓 I-4-07 学研究体相形成柱状相的两嵌段共聚物薄 6:20-6:40 李宝会南开大学膜在溶剂退火条件下自组装行为的 I-4-08 分子模拟研究 6:40-7:00 李伟南京大学大分子电子结构计算方法研究 I-4-09 7:00-7:20 I-4-0 7:20-7:35 O-4-0 李有勇 陈爽 苏州大学 南京大学 钙钛矿及碳硅复合等能源纳米材料的模拟 Ab Initio molecular dynamics simulations of nickel-catalyzed transformation of amorphous carbon into graphene in rapid thermal processing 7

207 年 月 9 日上午 主持人 : 李亚飞 陈雪波时间报告人单位题目 9:00-9:20 I-4-9:20-9:40 I-4-2 9:40-0:00 I-4-3 0:00-0:5 O-4-02 李震宇 崔刚龙 吴梦昊 尹兵 中国科学技术大学 北京师范大学 华中科技大学 西北大学 0:5-0:40 茶歇 Dominant kinetic pathways in CVD growth of graphene: hydrogen saturation induced edge stabilization 复杂体系的技法态电子结构和非 绝 热动力学 Chemically functionalized two-dimensional ferroelectrics/ multiferroics: combination of high-mobility semiconductors and non-volatile memory The combination of superhalogens and Brønsted acids HX (X=F, Cl, Br): An effective strategy for designing strong superacids 主持人 : 李震宇 崔刚龙 时间 报告人 单位 题目 0:40-:00 I-4-4 李亚飞 南京师范大学 新颖二维材料的设计与模拟 :00-:20 陈雪波 北京师范大学 Electron and energy transfer theory in I-4-5 :20-:40 I-4-6 :40-:55 O-4-03 巫瑞波 党丽 中山大学 汕头大学 207 年 月 9 日下午 visible-light photocatalysis 稠环倍半萜类天然产物生源机制的理论研究 Water assistant hydrogen evolution reaction (HER) catalyzed by molecular [MoS2] 2+ 主持人 : 郭洪霞 卢本卓时间报告人单位题目 3:30-3:50 I-4-7 3:50-4:0 I-4-8 4:0-4:30 I-4-9 王金兰 李晓霞 曾桂香 东南大学 中国科学院过程工程研究所 南京大学 Two-dimensional materials for electrocatalytic water splitting 大规模反应分子动力学模拟新进展 Theoretical study on E-ligand cooperative catalysis of Pincer-type phosphorus compound: anew mode of reaction 8

4:30-4:45 O-4-04 4:45-5:00 O-4-05 5:00-5:5 O-4-06 5:5-5:30 O-4-07 程龙玖 李斌 黄玉成 陈名扬 安徽大学 国家纳米科学中心 安徽师范大学 北京计算科学研究中心 5:30-5:50 茶歇 207 年 月 20 日上午 9 Quintuple super bonding between superatoms of metallic clusters Coarse-grained simulations of peptide aggregation by nanoparticle Layer-dependent electronic properties of phosphorene-like materials and phosphorene-based van der Walls heterostructures Structures and properties of the ultra-small TiO2and ZnO nanoparticles 主持人 : 王金兰 李晓霞时间报告人单位题目 5:50-6:0 中国科学院化学郭洪霞 I-4-20 研究所中国科学院计算 6:0-6:30 卢本卓数学与科学工程 I-4-2 计算研究所 6:30-6:50 I-4-22 6:50-7:0 I-4-23 7:0-7:25 O-4-08 7:25-7:40 O-4-09 聚苯乙烯粗粒化模型的构建 : 结构 热力学 动力学 在线计算化学 I: 分子静电计算与可视化 夏飞华东师范大学 Ras 蛋白超粗粒化模型的发展 胡茜茜 何奕 王寒露 南京大学 浙江大学 广东石油化工学院 Dynamics of carbon monoxide dissociation on Co( 0) Enhancing the oxidation of toluene with external electric fields: a reactive molecular dynamics study Ti-MWW 的量子化学研究 分子筛催化氧化硫化物 主持人 : 欧阳德芳 郑清川时间报告人单位题目 9:00-9:20 刘轶上海大学 First-principles evaluation of catalytic I-4-24 performance of zeolite 9:20-9:40 I-4-25 9:40-9:55 O-4-0 9:55-0:0 O-4- 李晖 尉涛 王会 北京化工大学 西安近代化学研究所 国家纳米科学中心 Hydrolysis of atmospheric molecules and ion-induced nucleation of aerosols clusters 五唑阴离子形成和分解机理的理 论 计算研究 The catalytic mechanism, improvement and design of nanozymes

0:0-0:30 茶歇 主持人 : 马晶 刘轶时间报告人单位题目 0:30-0:50 I-4-26 0:50-:0 I-4-27 :0-:25 O-4-2 :25-:40 O-4-3 :40-:55 O-4-4 欧阳德芳 澳门大学 Investigation molecular dissolution mechanism of ketoprofen ternary solid dispersions by molecular dynamics simulations 郑清川吉林大学分支酸酶家族产品调控机制的研究 顾芳 吴夏 河北大学 安庆师范大学 封闭球腔内氢键流体的界面张力研究 Co2Bn (n = - 8) 团簇几何结构的密度泛函理论研究 赵志坚天津大学烃类转化反应机理研究 20

第五分会分子模拟国际论坛 ( 二楼中大厅 Zhongda Hall) International Workshop on MolecularSimulations Nov. 8 th, 3:30-7:30 Zhongda Hall, NJUInternationalConferenceCenter Session chair: Wenchuan Wang, Beijing University of Chemical Technology 3:30-3:50 Nick Quirke, ImperialCollege The excess electron at interfaces 3:50-4:0 Xianren Zhang, BeijingUniversity of Chemical Technology Molecular simulations on biomembranes: non-equilibrium and anisotropy 4:0-4:30 Monte Pettitt, University of Texas Medical Branch DNA in confinement: Defining forces 4:30-4:50 Jian Zhou, SouthChinaUniversity of Technology Multiscale modeling and simulation of protein adsorption 4:50-5:0 Jiawei Shen, HangzhouNormalUniversity Molecular simulation of gene delivery systems 5:0-5:30 Coffee break Session chair:nick Quirke, Imperial College 5:30-5:50 Peter Cummings, VanderbiltUniversity Molecular studies of ionic liquids at interfaces with application to supercapacitors 5:50-6:0 Dongqin Wei, ShanghaiJiaotongUniversity Protein interaction and recognition 6:0-6:30 Jijun Zhao, DalianUniversity of Technology Novel structures and phase diagram of ices and hydrates 6:30-6:50 Fernando Bresme, ImperialCollege Microscopic origin of the thermal resistance at nanoscale interfaces 6:50-7:0 Huai Sun, ShanghaiJiaotongUniversity Predictions of thermodynamic properties using high-throughput molecular simulations 7:0-7:30 Mingjie Wei, NanjingTechUniversity Water flow inside polyamide reverse osmosis membranes: A nonequilibrium molecular dynamics study Nov. 9 th, 9:00-2:00Zhongda Hall, NJUInternationalConferenceCenter Session chair:peter Cummings, Vanderbilt University 9:00-9:20 Yuko Okamoto, NagoyaUniversity Classical and quantum molecular simulations in generalized ensemble 9:20-9:40 Dapeng Cao, BeijingUniversity of Chemical Technology Molecular simulation and experimental synthesis of nano-structured porous materials 9:40-0:00 Clare Mary McCabe, VanderbiltUniversity 2

Molecular simulation of skin lipids: Insights into barrier function 0:00-0:20 Shuangliang Zhao, EastChinaUniversity of Science& Technology Effects of kinetic dielectric decrement on ion diffusion and capacitance in electrochemical systems 0:20-0:40 Coffee break Session chair:yuko Okamoto, NagoyaUniversity 0:40-:00 Martin Sweatman, University of Edinburgh Growth and reproduction of giant SALR clusters, with implications for their reproduction :00-:20 Zhiguo Qu, Xi anjiaotonguniversity Adsorption mass transfer in porous media :20-:40 Debra J Bernhardt, The University of Queensland Ab initio nonequilibrium molecular dynamics simulations of transport properties :40-2:00 Li Zhang, Zhejiang Science and Technology University Understanding water desalination through nanotubes: A molecular dynamics simulations study 22

墙报展讲 Poster Session (First Floor) 时间 : 月 8 日晚 9:00-2:00 地点 : 南京大学国际会议 中心一楼紫金厅门口展区 第一分会 P--00 P--002 Suqing Li Tao Liang Exploring functions of long noncoding RNAs across multiplecancers through co-expression network A joint strategy applied to explore structural feathers of intermediate states in the activation process and their selections to ligands for GPCR P--003 畅东平数据挖掘辅助化学实验设计算法对比 P--004 陈可先香豆素类抗癌药物的定量构效关系研究 P--005 丁俊杰白蛋白与有机磷加合物位点识别及结构性质研究 P--006 杜宇 蛋白质机器与配体分子结合动力学的高效计算模拟及其应 用 P--007 段红霞靶标结构驱动的新烟碱类化合物的蜂毒机制研究 P--008 P--009 P--00 封婷 富炜涛 古江勇 HawkRank: A New Scoring Function for Protein-Protein Docking Based on Weighted Energy Terms Structure-based design and synthesis of L858R/T790M selective epidermal growth factor receptor inhibitors for NSCLC Inflammatory pathway network-based drug repositioning and molecular phenomics P--0 韩莉建立蛋白 - 蛋白分子对接打分函数的评价体系 P--02 P--03 金晔 孔晓天 MDBuilder: a program for the preparation of biomolecular simulations Type-I/2 型 ALK 抑制剂采用独特的 DFG-shifted 构象抑制 ALK 抗药性突变体 P--04 孔越基于配体的逐级虚拟筛选方法发现新型极光激酶抑制剂 P--05 雷太龙 Development of Quantitative and Qualitative Prediction Models for Chemical-Induced Respiratory Toxicity 23

P--06 李大禹钠离子通道位点 2 与激动剂作用机制分子模拟研究 P--07 李嫣 A Novel Fragment-Based Method for GPCR Ligand Design P--08 李杨 计算机辅助 HIV- 整合酶 LEDGF/p75 抑制剂生物活性预测研究 P--09 刘广斌基于 BRCA2 motif BRC8 的 RAD5 蛋白抑制剂的设计合成 P--020 P--02 刘清竹 刘志海 Discovery of Novel Non-Bisphosphonate FPPS Inhibitors by Multistage Docking- and Pharmacophore-Based Virtual Screening Forging the Basis for Developing Protein Ligand Interaction Scoring Functions P--022 卢凯亮数据挖掘辅助化学实验条件优化设计 P--023 路慧哲钠 - 葡糖共转运蛋白 2(SGLT2) 与其抑制剂的作用机理研究 P--024 尚俊 Comparative analyses of structural features and scaffold diversity for purchasable compound libraries P--025 佘柰 LDS 抑制剂设计与动力学研究 P--026 石丹枫 Understanding the structural and energetic basis of PD- and monoclonal antibodies bound to PD-L: a molecular modeling perspective P--027 石丽数据挖掘在钙钛矿光催化的应用 P--028 苏敏仪完善评价蛋白 - 配体打分函数性能的 CASF 方法体系 P--029 P--030 孙慧涌 孙丽霞 快速结合效应介导的 crizotinib 手性异构体在 MTH 结合过程中的差异性 Different multi-label strategies for the prediction of endocrine disrupting activity of environmental compounds P--03 王柠柠 ADMETlab: 一个系统的 ADMET 性质在线预测平台 P--032 P--033 王珊珊 王哲 Prediction of Binding Modes and Binding Affinities of Propanidid and AZD-3043 with the GABAA Receptor by Docking and ONIOM Calculations Comprehensive evaluation of ten docking programs on a diverse set of protein-ligand complexes: prediction accuracy of sampling power and scoring power P--034 肖林辉 Support Vector Regression Assisted Predictions of Néel 24

P--035 肖薇 temperature of ABO3 perovskites Statistical Analysis, Investigation, and Prediction of the Water Positions in the Binding Sites ofproteins P--036 徐潇数据挖掘在氟橡胶生产装置工艺优化中的应用 P--037 P--038 P--039 徐优俊 薛文杰 杨弘宾 Deep Learning Based Regression and Multi-class Models for Acute Oral Toxicity Prediction with Automatic Chemical Feature Extraction Discovery of LspA Inhibitors as Novel Antibacterial Agents: Virtual Screening, Synthesis and Biological Evaluation OrangeModeling-a tool for machine learning based quantitative structure-property relationship modeling P--040 杨启帆探讨评价打分函数中的统计问题 第二分会 P-2-00 P-2-002 P-2-003 P-2-004 付宏高剑高伟李颜 拉曼光谱成像结合多元曲线分辨测定紫外线对不同防护 条件下的皮肤损伤 Structure-based drug design of non-atp competitive small molecule inhibitor of Plk to treat cancer Theoretical Insights into Polymorphic Co-crystal of 5-Fluorouracil and 4- Hydroxybenzoic acid : Stability and Solubility 拉曼光谱成像技术结合化学计量学判别宫颈癌组织石蜡 切片 P-2-005 梁羽集成机器学习算法在癌症基因筛选及预后预测中的应用 P-2-006 P-2-007 刘鹏 刘晴 A variable selection method based on bat algorithm for near spectral analysis The label-free ratiometric fluorescent aptamer sensor based on the quantitative fluorescence model and dual wavelength monitoring for the detection of Pb 2+ in environment water samples P-2-008 刘言基于独立成分分析的多仪器模型转移方法 P-2-009 柳媛 Post-modified NMF 解卷积异质化临床样本以获得特定细胞类型的基因表达 25

P-2-00 马莎莎 Discrimination of Acori Tatarinowii Rhizoma from two habitats based on GC- MS fingerprinting and Lasso-PLS-DA P-2-0 邵常艳太赫兹光谱结合化学计量学鉴别木材种类研究 P-2-02 P-2-03 申琦 石彩霞 Combining the Suitability Score and Successive Projection Algorithm for Variable Selection in Partial Least-squares Discriminant Analysis Novel calibration models for quantification of DNA in biological samples by mass spectrometry based Exonuclease III-assisted recycling amplification P-2-04 孙禧亭 Adaptive Window Size Savitzky-Golay Smoothing P-2-05 P-2-06 P-2-07 P-2-08 P-2-09 王宇文明吴祺琤伍小云闫春华 VEGFR2 与药物分子的结合模式及作用机制的分子动力学模拟研究 DeepMirTar: a deep-learning approach for predicting human mirna targets 拉曼高光谱成像结合化学计量学分析绿豆萌发过程代谢 研究 Investigation on the binding mechanism of loratinib with the c-ros oncogene (ROS) receptor tyrosine kinase via molecular dynamics simulation and binding free energy calculations 激光诱导击穿光谱技术结合核极限学习机以及变量选择 方法用于煤灰分 挥发分以及热值的快速测定 P-2-020 杨林 C 8 H 8 同分异构与沸点的 QSPR 研究 P-2-02 印春凯基于结构模体和在线学习策略的蛋白质二级结构预测 P-2-022 P-2-023 P-2-024 于洋 张冰洋 张进 手机摄像系统结合化学计量学检测食品饮料中偶氮类色 素含量 The influence of class-imbalance ratio, data dimension and variable correlation for classification of metabolomics data 一种基于启发式最优伙伴波段组合的近红外光谱变量选 择方法 P-2-025 张秋兰孔雀石绿及其代谢产物与血清蛋白的作用过程研究 P-2-026 张若秋模型集群分析 (MPA) 结合最小绝对收缩和选择算子 26

(LASSO) 在光谱多元校正中的应用 P-2-027 张天龙大气污染物中多环芳烃致癌性的定性构效关系研究 P-2-028 P-2-029 P-2-030 张雪琴 赵义欢 周燕平 Surface-enhanced Raman spectroscopy based on Au-core/Ag-shell nanoparticles with embedded internal standard to quantify methimazole with Advanced Chemometri c Method Chemometrics-enhanced HPLC-DAD strategy for rapid quantification of seven nitroaromatic compounds in environmental water samples Bagging Classification Tree-Based Robust Variable Selection for Radial Basis Function Network in Metabonomics Data Analysis P-2-03 朱雪薇独立成分分析应用于温控近红外光谱数据的研究 P-2-032 朱艳丽 Quantitative analysis of enantiomers by multiplicative effects model and liquid chromatography-mass spectrometry P-3-00 P-3-002 P-3-003 戴中洋 丁明明 方国勇 第三分会 Understanding Structural Properties and Vibrational Spectra of Ethylammonium Nitrate Ionic Liquid Confined in TiO2 slits: The role of Hydrogen Bond Flow-Induced Polymer Translocation through a Nanopore from a Confining Nanotube Theoretical design and computational screening of precursors for atomic layer deposition P-3-004 关鑫超拉伸诱导结晶中的支化链作用 P-3-005 宋新毅通过分子模拟研究水在不同二维材料中的传递性质 P-3-006 汤子仟负载离子液体吸收二氧化碳的分子动力学模拟研究 P-3-007 王昆 The chain-growth of Ammoniaborane: The mechanism Study of the Dehydrogenation of a Traditional Lewis Pairs Catalyzed by Frustrated Lewis Pairs P-3-008 于玉琪 HIV- 蛋白酶构象变化机制及抗药性突变的影响 P-3-009 张力耘 基于碳纳米管 - 嗅觉受体生物传感器的分子设计和理论研究 27

P-4-00 P-4-002 P-4-003 Josh D Deetz 安小丽 别丽华 第四分会 Liquid Structure and Ion Formation in Magnesium Borohydride Electrolyte The mechanism of Vismodegib inhibition of Smo was investigated by MetaD method 单位点 DNA 甲基化对 C/EBPβ 转录因子与 DNA 特异性识别序列相互影响机制的分子动力模拟研究 P-4-004 蔡引江 原子团簇转变拓扑图的表征 P-4-005 陈淏川 扩展自适应偏置力方法在 PLUMED 中的实现 P-4-006 陈俊帆 嵌段溶液亲疏水性对共聚物纤维晶体生长速率的影响 P-4-007 陈自然 板状 蔻环衍生物电荷传输速率的量子化学计算 P-4-008 池波 DOX: 准确预测蛋白 - 配体结合构象的计算方法研究 P-4-009 杜双利 润滑或粘滞? 水对于轮烷运动的作用 P-4-00 冯霖 A DFT study on the mechanism of Rhodium-Catalyzed Regioselective Hydrothiolation of Allyl Amines P-4-0 付浩浩水对轮烷穿梭运动的润滑作用 P-4-02 傅应强 Simulation on tensile failure process of Irregular Nickel Nanorods based on the molecular dynamics method P-4-03 耿勇亮 Computer-aided Design of Organic Hole Transport Materials P-4-04 侯彦君两种倍他司汀类药物分子结构与药理特性研究 P-4-05 黄灏可迁移的聚合物粗粒化力场开发 P-4-06 P-4-07 P-4-08 菅薇 蒋景行 李鹏飞 A Density Functional Theory Study of Oxygen Vacancy Formation at the () Surface of γ-fe2o3 and (000) Surface of α-fe 2 O 3 Mechanistic Study in Functionalization of Quinolines: Patterns of Radical Regio-selective C-H Activation Calculation of the Potential of Mean Force of a High-level Hamiltonian from a Low-level One: A Combination of the Weighted Histogram Analysis Method and The rmodynamic Perturbation 28

P-4-09 P-4-020 P-4-02 李胤午 李志锋 梁玉洁 General Hydrogen Activation Modes for Novel LewisAcid Transition Metal (LA-TM) Catalysts Theoretical Investigation on Diaurate-Catalysis Through C(sp3)-H Activation 钯催化碘代芳烃, 苯甲酸酐和丙烯酸酯交叉偶联合成烯基化 芳香酮的反应机理研究 P-4-022 刘英哲炸药晶体与溶剂界面相互作用的分子模拟研究 P-4-023 P-4-024 P-4-025 P-4-026 罗令衡马丽爽彭诚乔曼 Theoretical Investigation of Ferroelectric Switching of Supramolecular Rotators 光敏化能量转移驱动的立体选择性环加成反应的机理研 究 IMPROVING THE CORRELATION BETWEEN PREDICTED AND DETERMINED BIOACTIVITIES Tetra-silicene: A Semiconducting Allotrope of Silicene with Negative Poisson s Ratios P-4-027 任强表面活性剂与油水界面的介观模拟研究 P-4-028 屠晶 杂芳基二氢嘧啶类抑制剂与 HBV 的构效关系和作用机制研究 P-4-029 王桂敏阴离子 阴离子型卤键作用的理论研究 P-4-030 王涵 Experimental and Theoretical Studies of the Reactions of Ground-State Sulfur Atoms with Hydrogen and Deuterium P-4-03 王季平聚合物拉伸应力松弛的蒙特卡罗分子模拟 P-4-032 王静 DFT study on the mechanism of carbon dioxide activation by transition metal complexes P-4-033 王娟娟 光诱导电子转移调控的 C-H 官能团化反应机理研究 P-4-034 王彧 Quasi-Planar Pentacoordinate Silicon in CaSi Monolayer P-4-035 王钰璋 嵌段共聚物溶剂蒸发退火成胶束的分子动力学模拟 P-4-036 席建英 The charge transfer at the interface of dye@g/at(0) P-4-037 向衍 全氟代烷烃全原子力场开发 P-4-038 徐承欢 高分子冷结晶行为的蒙特卡罗分子模拟 29

P-4-039 徐飞基于 LPL 的泽泻醇调脂分子机制研究 P-4-040 P-4-04 P-4-042 徐丽娜 徐先燕 徐永鑫 Supramolecular Catalysis in the Methylation of meta-phenylene Ethynylene Foldamer Containing N, N-Dimethylaminopyridine Probing Electric Field Effect on the catalytic performance of Mn-doped Graphene to COoxidation Theoretical Study of Organic Sensitizers for High Efficient D A π A Dye- Sensitized SolarCells P-4-043 杨东春 Novel carbon nanotubes from 6,6,2-Graphyne P-4-044 杨文静 Nonadiabatic Curve-crossing Model for Single Electron Transfer in Visible- Light Photoredox Catalysis P-4-045 杨溢龙 Deep learning for pharmaceutical formulation prediction P-4-046 叶仁龙 Elucidating the host-guest binding mechanisms by the molecular dynamics/quantum mechanics/continuum solvent model approach P-4-047 张宏不同力场对 DNA 构型转变的影响 P-4-048 P-4-049 张家华 张晓敏 DFT Study on C-H Amination Reactions Catalyzed by Iron Porphyrin Nitrene Compounds with Different Nitrogen Sources Theoretical Insight into C(sp3)-F Bond Activations and Origins of Chemo- and Regio-selectivities of Tunable Nickel-Mediated/Catalyzed Couplings of 2-Triflu oromethyl--alkenes with Alkynes P-4-050 张晓蕊光诱导电子转移调控的双催化 [2+2] 环加成反应机理研究 P-4-05 赵云震压差驱动下水和离子穿越碳纳米管的输运行为 P-4-052 P-4-053 周双艳 周晓雨 Exploration of the ph-induced misfolding mechanism of prion protein: insight from molecular dynamics simulations and Markov state model analysis DFT Study on the Mechanistic Insights into the Hydrolysis of BNPP Catalyzed by Mononuclear zinccomplexes 30

地铁 2 号线南京大学仙林校区站至会场及各酒店的路线图

主 NSCCC 中国化学会 207 c 会议论文及海报摘要 承办 : 计算机化学专业委员会 南京大学化学化工学院 协办 : 南京大学理论与计算化学研究所 配位化学国家重点 实验室 生命分析国家重点实验室 高性能高分子材料与技 术教育部重点实验室和江苏省化学化工学会 支持单位 :AIP Publishing 北京并行科技股份有限公司广州景派科技有限公司 梅特勒 - 托利多国际贸易 ( 上海 ) 有限公司 33

PL0 生命化学前沿及发展机遇 陈洪渊 南京大学 34

PL02 My view on the biological importance of charged systems 杨玉良 复旦大学 35

PL03 理论计算驱动的药物研究 蒋华良 中国科学院上海药物研究所 36

PL04 基于结构的药物设计 : 挑战和机会 吴国胜 康龙化成 ( 北京 ) 新药技术股份有限公司北京市泰河路 6 号, 0076 Email: guosheng.wu@pharmaron.com 几十年来, 基于靶点结构的计算机辅助药物设计一直是新药发现领域非常重要的工具, 但是目前的方 法仍然满足不了实际应用的需求 其中主要的难点在于如何准确预测分子的生物活性, 以及产生新颖的容 易合成的分子 我们将结合大量的实例, 讨论这一领域的一些常见的问题和可行的策略 关键词 : 药物设计, 靶点结构, 分子模拟 37

PL05 化学计量学助推分析化学研究范式转换 Chemometrics-assisted Research Paradigm Transit for Analytical Chemistry 俞汝勤 ( 湖南大学化学化工学院化学生物传感与计量学国家重点实验室长沙 rqyu@hnu.edu.cn) T. Kuhn 962 年在 科学革命的结构 一书中提出科学研究 范式 概念 J.Gray 2007 年发表有关科学研究四种范式的演讲 四种范式是指经验科学 理论科学 计算科学和数据 ( 密集型 ) 科学 本报告先讨论经验科学向理论科学演进中化学与分析化学遇到的 数学化 问题, 进而探讨化学计量学在助推分析化学完善 数学化 进程中同时实现其 信息化, 步入第三即计算科学范式 在 数据海啸 背景下, 作为产生分析数据的主要贡献者, 分析化学在化学计量学协助与推动下, 正步入第四即 数据密集型知识发现 的数据科学新范式 38

PL06 计算化学在中药研究中的应用 徐筱杰 北京大学 39

PL07 从基于结构到基于系统的药物设计 来鲁华 北京大学 40

PL08 Forging the basis of developing protein-ligand interaction scoring functions 王任小 中国科学院上海有机化学研究所 4

PL09 基于靶点结构的虚拟筛选中个性化策略的探讨 侯廷军 浙江大学 42

I--0 基于系统生物学的中药机理研究 来鲁华 * 北京大学化学与分子工程学院, 定量生物学中心, 生命科学联合中心, 北京,0087 *Email: lhlai@pku.edu.cn 癌症 炎症 糖尿病等复杂疾病由多种基因与环境作用所导致, 所涉及的生物分子间存在着复杂的作用和调控关系, 对于其中一种生物分子的调控会在网络水平上带来连锁效应, 因此需要从整体上理解相关生物网络的调控机理, 并在此基础上发展出高效的组合调控方案 中药的配伍方式表明通过同时调控多种靶标可以达到治疗或缓解疾病的效果, 系统生物学的发展为揭示中药的分子机理提供了新的机遇 我们针对疾病相关网络开展了系统生物学研究, 提出了针对疾病相关分子网络寻找关键结点和最优控制方案的方法, 发展了多种多靶标药物设计方法, 并将所建立的分子网络用于研究相关中药的分子作用机理 针对新型靶标, 我们发展了基于草药水平的虚拟筛选方法及实验研究, 在多种靶标体系中发现了具有活性的草药与化合物 将介绍报告人实验室的相关研究进展, 并讨论系统生物学的发展对于中药研究所带来的机遇与挑战 关键词 : 系统生物学 ; 中药 ; 生物网络 ; 分子机理 ; 多靶标药物设计参考文献 [] Pei, J.; Yin, N.; Ma, X.; Lai, L. J. Am. Chem. Soc. 204, 36: 556. [2] Meng, H.; Liu, Y.; Lai, L. Acc. Chem. Res. 205, 48: 2242. [3] Liang, H.; Ruan, H.; Ouyang, Q.; Lai, L. Sci. Rep. 206, 6:36767. [4] Gu, S.; Yin, N.; Pei, J.; Lai, L. Mol. Biosyst. 203, 9: 2696. [5] Gu, S.; Yin, N.; Pei, J.; Lai, L. Mol. Biosyst. 203, 9: 93. 43

I--02 新型 ALK 抑制剂的设计和优化 侯廷军 浙江大学药学院 浙江省杭州市 30058 Email: tingjunhou@zju.edu.cn 间变性淋巴瘤激酶 ALK 蛋白是一种受体酪氨酸激酶 属于胰岛素受体超家族 是EML4-ALK融合 型非小细胞肺癌的关键治疗靶点 目前所有针对ALK的临床实验药物对ALK中多种且大量出现的耐药性突 变的治疗效果仍然不佳 因此 寻找针对ALK的抗耐药抑制剂迫在眉睫 我们设计合成了一系列新型的 Type-I/2型ALK抑制剂 它们同时占据ATP结合位点以及邻近的别构位点 而且改变 DFG 的构象 激酶 和细胞活性评价表明 化合物00-07比已经上市的crizotinib和ceritinib具有更优的抑制活性 此外 00-07 对L96M C56Y R275Q和F74L ALK相关的耐药细胞系均有很高的抑制活性 此外 除LTK和ROS, 00-07对其他33个不同家族的激酶均没有明显的抑制效果 显示了00-07的高选择性 Fig. Rational design of possible "bridge molecules" that Fig. 2 Inhibitory activities of the synthesized type-i/2 could target both ATP-binding site and back pocket. inhibitors. 关键词 Type-I/2 ALK抑制剂 DFG-shifted 抑制活性 抗药性突变 选择性 参考文献. Sun HY, Pan PC, Tian S, Xu L, Kong XT, Li YY, Li D, Hou TJ*, Constructing and Validating High-Performance MIEC-SVM Models in Virtual Screening for Kinases: A Better Way for Actives Discovery, Sci. Reports, 206, 6, 2487. 2. Kong XT, Pan, PC, Li D, Tian S, Li YY, Hou TJ*, Importance of protein flexibility in ranking inhibitor affinities: modeling the binding mechanisms of piperidine carboxamides as Type I/2 ALK inhibitors, Phys. Chem. Chem. Phys., 205, 7, 6090. 3. Sun HY, Li YY, Li D, Hou TJ*, Insight into Crizotinib Resistance Mechanisms Caused by Three Mutations in ALK Tyrosine Kinase using Free Energy Calculation Approaches, J. Chem. Inf. Model., 203, 53, 2376. 4. Pan P, Yu HD, Liu Q, Kong X, Huang Y, Hou TJ*, Combating Drug-resistant Mutants of ALK with Potent and Selective Type-I/2 Inhibitors by Stabilizing Unique DFG-shifted Loop Conformation, 207, submitted. 44

I--03 基于 Tph- 的抗骨质疏松分子的设计, 合成与活性 李建新 南京大学 45

I--04 Computational design aminergic GPCR agonists/antagonists Wei Fu Department of Medicinal Chemistry & Key Laboratory of Smart Drug Delivery, Ministry of Education, School of Pharmacy, Fudan University, Shanghai 20203, China G-protein-coupled receptors (GPCRs) comprise the largest class of therapeutic targets that aimed by approximately 45% of modern medicinal drugs. Dopamine, serotonin and opioid receptors belong to A-class GPCRs related to mental disorders and pain. As a robust approach, computer-aided drug design (CADD) has been demonstrated to be a powerful tool to discover novel drugs against these disorders and to help understand the activation mechanism of related receptors. Herein, variety of computational and drug design techniques were integrated in this study with the eventual aim to develop novel superior antipsychotic agents and analgesia with less side effects and tailor these agents to possess the designed properties for individual therapy. Key words: GPCRs; Drug design; dopamine receptor, serotonin receptor; opioid receptor 46

I--05 A systematic review of reverse screening methods in search for protein targets of chemopreventive compounds Hongbing Huang, Guigui Zhang, Yuquan Zhou, Chenru Lin, Suling Chen, Shangkang Mai, Yutong Lin, Zunnan Huang * Dongguan Scientific Research Center, Key Laboratory for Medical Molecular Diagnostics of Guangdong Province, Guangdong Medical University, Dongguan, Guangdong 523808, China *Email: zn_huang@yahoo.com This presentation is an invited review of reverse screening methods to search for protein targets of chemopreventive compounds or drugs. The typical chemopreventive compounds include traditional Chinese medicine, FDA approved drugs, and nature compounds etc. They are selective but are predisposed to bind multiple protein targets distributed throughout diverse signaling pathways in human cells. In contrast to the conventional virtual screening for finding the ligands of a targeted protein from a compound database, reverse screening is used to identify the potential targets or off-targets of a given chemopreventive compound from a large number of receptors through their known ligands or crystal structures. Reverse screening, also known as in silico or computational target fishing, is very useful in discovering the target receptors of the query molecules from terrestrial or marine natural products, exploring the molecular mechanisms of the chemopreventive compounds, finding alternative indications of existing drugs by drug repositioning, and detecting adverse drug reactions and drug toxicity. It can be divided into three major groups of computational methods as shape screening, pharmacorphore screening and reverse docking. For these computational methods, a number of large software packages such as Schrodinger and Discovery Studio, typical software / network services such as INVDOCK, ChemMapper, PharmMapper and idtarget, practical databases of known target ligands or receptor crystal structures such as Ligand Expo3 database, ChEMBL database and scpdb are available. Different programs, network services and databases have different ranges of application and constraints. Here we carried out a systematic analysis and a multilevel classification of the computational programs, network services and compound libraries for shape, pharmacorphore screening and reverse docking used in the process of protein target fishing. In addition, we reviewed the main features of these methods, programs and databases, and further provided a variety of application examples to use one or more reverse screening methods for accurate target predictions. This presentation was supported by the Natural Science Foundation of Guangdong Province, China (205A0303358), Provincial Major Project of Basic or Applied Research in Natural Science, Guangdong Provincial Education Department (206KZDXM038), and 203 Sail Plan "the Introduction of the Shortage of Top-Notch Talent" Project (YueRenCaiBan [204] ). Keywords: Drug Design, Reserve Screening, Shape Screening, Pharmacorphore Screening, Reverse Docking References: [] Jenkins, J. L., Bender, A., Davies, J. W. Drug Discov Today Technologies. 2006, 3(4): 43-42. [2] Koutsoukas, A., Simms, B., Kirchmair, J., Bond, P. J. J. Proteomics. 20, 74: 2554 2574. [3] Zheng, M., Liu, X., Xu, Y., Li, H., Luo, C., Jiang, H. Trends Pharmacol Sci. 203, 34(0): 549. [4] Wang, L., Xie, X. Q. Future Med Chem. 204, 6:247 249. [5] Cereto-Massagué, A., Ojeda, M. J., Valls, C., Mulero, M. Methods. 205, 7: 98. [6] Lee, A., Lee, K., Kim, D. Expert Opin Drug Dis. 206, :7 47

I--06 Supramolecular interaction between insulin and Cp- peptide and their assembly as rapid-acting formulation Yantao Chen *, Jianshu Li 2 College of Chemistry and Environmental Engineering, Shenzhen University, Shenzhen, P.R. China 2 College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, P.R. China *Email: ytchen@szu.edu.cn It has been of significant interest to develop rapid-acting insulin formulations that mimic the physiological meal-time profile of human insulin. As Insulin is easy to form aggregates which cannot work well in blood, a supramolecular strategy is presented in this work with the employment of a fragment of C-peptide (Cp-). In vitro experiments demonstrated that effective inhibition of insulin aggregation has been achieved by the addition of Cp- peptide. Co-infusion of insulin and Cp- peptide in diabetic rats resulted in a more rapid onset and more marked hypoglycaemia than insulin alone. Computer simulation indicated that Cp- can insert into the space between C-terminal tail and N-terminal helix of insulin s B-chain, resulted in a transition from close state to open state for insulin conformation. The appearance of open state not only leads to the dissociation of insulin dimer, but also facilitates the quick binding of insulin with insulin receptor by lowering the free energy barrier. These results suggest that Cp- peptide may find its role in the development of an effective rapid-acting strategy for diabetes therapy. Fig. Supramolecular interaction between Cp- and insulin. Cp- can prevent the aggregation of insulin and form supramolecular assembly of Cp- and insulin (SACI), which will release monomeric insulin Keywords: Insulin formulation; Molecular simulation; Supramolecular interaction; 3D structure; Binding energy References: [] Wang, W.; Li, S.; Zhao, Z.; Zhou, A.; Liu, Y.; Chen, Y.; Lin, M.; Chen, G.; Ding, C.; Li, J. J. Bioresources & Bioproducts. 207: Accepted 48

I--07 New Efficient Methods for Sampling Protein Conformation Weiliang Zhu Drug Discovery and Design Centre, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchognzhi Road, Shanghai 20203 *Email: wlzhu@simm.ac.cn Protein may have different conformations, and its function is highly correlated with its conformational change. However, it is a great challenge to sample protein conformations as its space is enormous, which requires huge computer resources. In order to improve the efficiency of protein conformation sampling, we developed two new methods for sampling protein conformation with higher efficiency than existing algorithm. The application of the new methods on some protein systems demonstrated that the computational and conformation sampling efficiency is improved significantly. Keywords: protein conformation; MD simulation; enhanced sampling method 49

I--08 关于化学信息学应用与发展的若干思考 徐雯丽, 黄迎, 李佳, 胡静, 蒋舒仰, 姚建华 * 中国科学院上海有机化学研究所, 上海市零陵路 345 号,200032 *Email: yaojh@sioc.ac.cn 化学 (Chemistry) 是研究物质的组成 结构 性质和变化规律的科学 [], 其研究内容主要可归纳为三部分 : 分子设计 合成设计及化合物结构确定 2003 年, 以色列化学家 Arnon Shani 发表了一篇题为 化学无处不在 的文章 [2],203 年, 徐光宪先生在中国科学报上发表题为 第六次科技革命的内涵 的文章 [3], 这两篇文章都明确阐述了化学的本质 应用领域和作用 : 除了数学外的学科领域很多问题, 其本质是化学问题 化学信息学是利用信息学方法和技术解决化学问题的学科 [4], 它是计算机科学 数学与化学交叉组合后形成的交叉学科 化学信息学方法主要有三种 : 基于数据 基于逻辑和基于原理 鉴于药物设计 农药设计 食品科学 环境科学 材料科学和公共安全等领域都存在对应的化学问题, 因此, 化学信息学方法和技术可应用于辅助这些领域中的分子设计 合成设计及化学结构确定工作 由于不同领域中, 化学问题表现形式不同, 因此, 合理转化表现形式为对应的化学问题, 是有效应用化学信息学方法和技术的关键 在此, 我们将通过实例, 介绍转化的策略和方法 随着化学研究的深入, 实验及其测试技术不断发展, 实验所产生的数据量增长速度极快 由于数据量的快速增大, 我们应该关注化学信息学中常用的化学数据分析策略和方法的适用性 为了满足相关领域学科发展的需要, 化学信息学的方法研究内容必须有所拓展 如, 必须关注需要解决的问题在化学上的不同表现形式, 化学与应用领域学科之间的关系, 分析问题的本质, 实现合理转化 这些或许将成为化学信息学新方法的研究内容 本报告, 将就此作详细的讨论 关键词 : 化学信息学 ; 数据分析 ; 问题转化 参考文献 [] http://chemweb.ucc.ie/what_is_chemistry.htm. Retrieved 207-08-0 [2] Arnon Shani, Chem. Edu. Inter., 2003, Vol. 4, No.. [3] 徐光宪, 中国科学报,203-4- [4] J. Gasteiger, T. Engel, Chemoinformatics, A Textbook, WILEY-VCH, 2003. 50

I--09 Multiple-levels potential-energy- surfaces crossing (MSC) strategy for accurate prediction of the complex molecular conformations with lower- energy-states 万坚华中师范大学 5

I--0 抗雄激素类前列腺癌治疗药物耐药机制的理论研究及新型 雄激素受体拮抗剂的筛选李加忠 *, 刘宏丽, 王灵燕, 宋田青 兰州大学药学院, 甘肃省兰州市东岗西路 99 号,730000 *Email: lijiazhong@lzu.edu.cn 前列腺癌是发生于男性前列腺组织中的恶性肿瘤, 在欧美等发达国家和地区, 它是男性最常见的恶性肿瘤, 其死亡率居各种癌症的第二位 [] 在亚洲, 其发病率低于西方国家, 但近年来呈迅速上升趋势 雄激素受体 (Androgen receptor, AR) 是治疗前列腺癌的重要靶标 [2], 使用雄激素受体拮抗剂阻断内源性雄激素与 AR 的结合能够达到治疗目的 常用的雄激素受体拮抗剂有恩杂鲁胺 (Enzalutamide) 比卡鲁胺 (R-bicalutamide) 和羟基氟他胺 (Hydroxyflutamide) 等, 但这些药物在临床使用一段时间后均会产生耐药性,AR 突变是产生耐药性的主要原因 [3] 从去势抵抗性前列腺患者的组织样本中发现了一系列氨基酸突变的 AR, 如 :L70H, W74C, W74L, H874Y, F876L,T877A 和 M895T 等 ( 如图一所示 ), 这些突变都位于 AR 的配体结合域 (Ligand-Binding Domain LBD) 我们通过分子模拟和自由能计算, 从分子水平上研究了以上三个主要药物与雄激素受体 ( 野生型和突变体 ) 的结合作用模式, 阐明了可能的耐药机制 [4-6] 结果表明, AR 中的螺旋 2(H2, 像一个盖子置于 LBD 顶部 ) 在耐药机制中起着关键作用 当 enzalutamide 的 C 环 R-bicalutamide 的 B 环或羟基氟他胺靠近 H2 时, 阻止 H2 闭合并扭曲了共激活剂结合位点, 从而导致无效的转录, 药物起到拮抗作用 相反, 当 B 或 C 环靠近 H 或 Loop-2, 有利于 H2 闭合形成共激活剂结合位点, 则拮抗剂转变为激动剂, 产生耐药性 根据此耐药机制, 我们研究了筛选得到的潜在的 AR 拮抗剂与突变体雄激素受体的作用模式, 分析了 AR 拮抗剂解决耐药性的可能性 Fig. The possible amino acid mutations located in the AR LBD and the movement of helix H2. 关键词 : 雄激素受体 ; 拮抗剂 ; 耐药性 ; 分子动力学模拟 ; 虚拟筛选参考文献 [] Center, M. M.; Jemal, A.; Lortet-Tieulent, J.; Ward, E. European urology, 202, 6:079. [2] Balk, S. P. Urology, 2002, 60: 32. [3] Taplin, M. E.; Bubley, G. J.; Shuster, T. D.; Frantz, M. E. N. Engl. J. Med.995, 332, 393. [4] Liu, H.L.; Wang, L.Y.; Song, T.Q.; Li, J.Z.; Liu, H.X. J. Cell. Biochem. 207, 8, 2792. [5] Liu, H.L.; Han, R.; Li, J.Z.; Liu, H.X.; Zheng, L.F. J. Comput. Aid. Mol. Des. 206, 30, 89. [6] Liu, H.L.; Zhong, H.Y.; Song, T.Q.; Li, J.Z. Int. J. Mol. Sci. 207, Accepted. 52

I-- On the Theory of Comparing Two Models with Correlation Coefficients Qi-Fan Yang( 杨启帆 ), Ren-Xiao Wang ( 王任小 ) * 中国科学院上海有机化学研究所, 生命有机化学国家重点实验室, 上海市徐汇区零陵路 345 号, 邮编 200032 *Email: wangrx@mail.sioc.ac.cn Abstract: The quality of a computational model, e.g. a scoring function for computing protein-ligand binding affinity, is often measured by the correlation coefficient (R) between experimental data and the computed values. In order to compare the performance of two models, one needs to consider the R values produced by them as well as the sample size to derive a meaningful hypothesis. Recently, Carlson et al. published an analysis on this issue (J. Chem. Inf. Model. 203, 53, 837-84), and they came to an astonishing conclusion that current available data sets were simply too small for testing scoring functions at an acceptable confidence level. In this study, we examined this issue and found that Carlson et al had misinterpreted their analysis results. Besides, it is more appropriate to apply Meng's method for comparing correlated correlation coefficients (Psychological Bulletin, 992,, 72-75) to this analysis. Our analysis reveals that: () A larger data set is required if there is only a subtle difference between the R values of two models. (2) A larger data set is required if the R values of two models are at a lower level. (3) If the inter-correlation between the outcomes of two models is low, a large data set of several hundred to several thousand samples is required; otherwise, a smaller data set of several dozen samples is required. A numerical simulation was conducted, which verified that our results were consistent with the theoretical prediction; whereas Carlson's results were not. Fig. Required sample size for comparing two models at a given confidence level varies with the correlation coefficients generated by the two models as well as the inter-correlation between them. 关键词 : Pearson correlation coefficient, test statistics, sample size, confidence level 参考文献 : [] Heather A. Carlson, Check Your Confidence: Size Really Does Matter, J. Chem. Inf. Model. 203, 53, 837 84. [2] Meng, X. L.; Rosenthal, R.; Rubin, D. B., Comparing Correlated Correlation-coefficients. Psychol. Bull. 992,, 72-75. 53

I--2 Veratramine modulates AP--dependent gene transcription by directly binding to programmable DNA Honglin Li,* Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 30 Meilong Road, Shanghai, 200237 *Email: hlli@ecust.edu.cn ABSTRACT: Activator protein (AP-) is a transcription factor that regulates a variety of protein-encoding genes, it is a participant in many cellular functions, including proliferation, transformation, epithelial mesenchymal transition (EMT), and apoptosis. Inhibitors targeting AP- have potential use in the treatment of cancer and other inflammatory diseases 2. Strategy that identifies specific DNA-binding agents which blocks AP- binding to cognate DNA sequences is very effective and offers several advantages, i.e., inhibiting or affecting the function of whole families of transcription factors that share highly conserved DNA sequence domains. This would allow the regulation of only a subset of genes controlled by the given transcription factor without affecting the expression of the entire set of genes. In this study, we performed a virtual screening with our in-house DNA-specific molecular docking method idnabinder to search a natural database, and we identified veratramine as a potent natural modulator of AP-, which selectively binds to a specific site (TRE 5`-TGACTCA-3`) of the AP- target DNA sequence and regulates AP--dependent gene transcription without interfering with cystosolic signaling cascades that might lead to AP- activation. This discovery exemplifies the efficiency of our idnabinder protocol in the design of specific DNA-binding agents, which challenges the selectivity for short nucleic acid sequences that may be abundant in the human genome. Furthermore, a series of in vitro experiments indicate that veratramine acts on the downstream signaling of AP-, but does not interfere with the EGF-induced cytosolic MAPK signaling cascades or other AP- activation-related kinases. This indicates that the gene modulation occurs only on a subset of genes controlled by AP-. Moreover, RNA-seq experiments demonstrate that veratramine does not act on the Hedgehog signaling pathway in contrast to its analogue, cyclopamine, and possibly does not harbor the same teratogenicity and toxicity. Additionally, veratramine effectively suppresses EGF-induced AP- transactivation and transformation of JB6 P+ cells. Finally, we demonstrate that veratramine inhibits solar-ultraviolet-induced AP- activation in mice. The identification of veratramine and new findings in its specific regulation of AP- downstream genes pave ways to discovering and designing regulators to regulate transcription factor. Additionally, this study reveals that the modulator of specific regulation of stem cells. transcription factor could have a potential application in Keywords: veratramine, natural product, transcription factor, AP- References: [] Shaulian E, Karin M. Nature cell biology, 2002, 4(5): E3-E36. [2] Matthews C P, Colburn N H, Young M R. Current cancer drug targets, 2007, 7(4): 37-324. 54

I--3 数据驱动的药物设计方法学及应用研究 郑明月,*, 蒋华良,2,*, 陈凯先,2 中国科学院上海药物研究所药物发现与设计中心, 上海市浦东新区祖冲之路 555 号 20,20203 2 上海科技大学, 生命科学与技术学院,20003 *Email: myzheng@simm.ac.cn; hljiang@simm.ac.cn 当前, 各种生物医药数据以前所未有的速度增长, 如何更好的利用这些数据和信息, 深入理解药物作用的复杂生物过程, 提高先导化合物发现的效率, 并提升候选化合物的安全性和有效性, 是目前和今后创新药物研发的重要研究内容 我们主要围绕药物靶标 - 配体相互作用评价 药物靶标预测以及早期 ADME 性质和毒副作用评价等方面, 开展数据驱动的药物设计方法学发展和应用研究 随着数据积累 计算水平及分析手段的不断发展, 基于大规模数据的药物设计方法有望成为创新药物研究快速发展的关键推动力之一 关键词 : 药物设计 ; 虚拟筛选 ; 机器学习 ; 结构活性关系 ;ADMET 参考文献 [] Xu, Y., et al. J Med Chem 207, 60 (7): 2973. [2] Wang, Y., et al. J Med Chem 207, 60 (5): 2026. [3] Xing, J., et al. J Chem Inf Model, 207, 57 (7): 677. [4] Lu, J., et al. Biochim Biophys Acta, 206, 860 (): 2664. [5] Wang, Y., et al. Q Rev Biophys, 205, 48 (4): 488. [6] Liu, X., et al. Bioinformatics, 205, 3 (2): 2049. 55

I--4 高性能计算支持下的药物分子设计学 : 进展与展望 HPC-Supported Drug Design Methodology: Progresses & Perspectives Jun Xu Research Center for Drug Design (RCDD), School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 50006, China Abstract Pharmaceutical innovations involve in design, manufacture, and biologically validate the functions of small- and macro-molecules against specific diseases. Making or assaying these molecules are costly and time-consuming. In past decades, many algorithms have been developed to expedite the innovation processes and reduce the costs. These biomolecules are mathematically expressed in topological, steric, and static levels, which have different types of computational complexities. This talk will outline the algorithm problems in this field, summarize the progresses on HPC accelerated algorithms for pharmaceutical innovations in the author s team. The algorithms, such as, subgraph such/match algorithms, high frequent substructure deriving algorithm, virtual high throughput screening algorithms, virtual compound library generation algorithms, compound library generation algorithms, and artificial intellectual algorithms for druggability predictions, and their parallelization are specifically discussed in this lecture. Case studies on drug design or virtual screening using machine learning approaches, such as, naїve Bayesian classification, support vector machine and recursive petitioning, are presented. Biomedical big data processing technology including parallelized and GPU-accelerated molecular dynamics simulation technology, enhanced molecular docking technology, new parallelized algorithms for shape-based virtual screening, and free energy landscape calculations will be discussed. It is expected that the future developments in this field will focus on the new modeling methodologies capable of handling big data created from high throughput scientific experiments (screening and manufacturing), high performance computations (parallel computing based molecular simulation), medical information (such as medical record and health information) automation, and scientific publication/patent literature digitalization. 56

I--5 药物安全性的计算机预测研究 唐赟 * 华东理工大学药学院, 上海市新药设计重点实验室, 上海 200237 *Email: ytang234@ecust.edu.cn 药物安全性是临床应用药物的基本属性 由于安全性问题, 许多候选药物在开发阶段就面临失败, 同时也有许多上市药物被迫退市 药物安全性通常在临床前和临床试验阶段才进行实验评价, 然而, 体内和体外的实验评价既昂贵又费时, 一些慢性毒副作用还很难在短时间内通过实验确定 因此, 利用互联网上累积的大量安全性相关实验数据, 计算机预测技术已被广泛应用于药物安全性评价之中 计算机预测药物安全性, 不但具有绿色 快速 准确的优点, 而且可以在药物研发的早期进行 近几年来, 我们开发了一种基于子结构模式识别的计算机预测方法 [], 用分子指纹描述分子, 用机器学习方法建立分类模型 进一步采用信息增益 (IG) 技术, 以识别警示子结构, 这有助于解释模型和对分子进行结构改造 利用所发展的方法, 我们收集了大量相关数据集, 并建立了多种药物安全性的分类预测模型, 包括 Ames 致突变性 致癌性 急性口服毒性 herg 心脏毒性 肝脏毒性 内分泌干扰毒性等 [2-7] 这些模型已整合到我们的在线预测服务系统 admetsar 中 (http://lmmd.ecust.edu.cn/admetsar/), 可免费使用 [8] 本报告将主要介绍我们在药物安全性预测方面已取得的研究进展, 目前我们还在构建更多的药物安全性预测模型, 并正在对预测服务系统进行版本升级 关键词 : 药物安全性 ; 计算机预测 ; 分子指纹 ; 机器学习 ; 警示子结构 参考文献 [] Shen, J.; Cheng, F.; Xu, Y.; Li, W.; Tang, Y. J. Chem. Inf. Model. 200, 50(6): 034-04. [2] Xu, C.; Cheng, F.; Chen, L.; Du, Z.; Li, W.; Liu, G.; Lee, P. W.; Tang, Y. J. Chem. Inf. Model., 202, 52(): 2840-2847. [3] Li, X.; Chen, L.; Cheng, F.; Wu, Z.; Bian, H.; Xu, C.; Li, W.; Liu, G.; Shen, X.; Tang, Y. J. Chem. Inf. Model., 204, 54(4): 06-069. [4] Chen, Y.; Cheng, F.; Sun, L.; Li, W.; Liu, G.; Tang, Y. Ecotoxicol. Environ. Safety, 204, 0: 280-287. [5] Li, X.; Du, Z.; Wang, J.; Wu, Z.; Li, W.; Liu, G.; Shen, X.; Tang, Y. Mol. Inform. 205, 34(4): 228-235. [6] Zhang, C.; Zhou, Y.; Gu, S.; Wu, Z.; Wu, W.; Liu, C.; Wang, K.; Liu, G.; Li, W.; Lee, P. W.; Tang, Y. Toxicol. Res. 206, 5(2): 570-582. [7] Zhang, C.; Cheng, F.; Li, W.; Liu, G.; Lee, P. W.; Tang, Y. Mol. Inform., 206, 35(3-4): 36-44. [8] Cheng, F.; Zhou, Y.; Li, W.; Shen, J.; Wu, Z.; Liu, G.; Lee, P. W.; Tang, Y. J. Chem. Inf. Model., 202, 52(): 3099-305. 57

I--6 新型抗肺动脉高压 PDE5 抑制剂的设计与优化 罗海彬中山大学 58

I--7 ADReCS-Target: target profiles for aiding drug safety research and application Li-Hong Huang, Qiu-Shun He, Ke Liu, Jiao Cheng, Min-Dong Zhong, Lin-Shan Chen, Zhi-Liang Ji, * State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian, 3602, PR China *Email: appo@xmu.edu.cn Delivering safe and effective therapeutic treatment to patients is one of the grand challenges in modern medicine. However, drug safety research has been progressing slowly in recent years, compared to other fields such as biotechnologies and precision medicine, due to the mechanistic complexity of adverse drug reactions (ADRs). To fill up this gap, we develop a new database, the Adverse Drug Reaction Classification System-Target Profile (ADReCS-Target, http://bioinf.xmu.edu.cn/adrecs-target), which provides comprehensive information about ADRs caused by drug interaction with protein, gene and genetic variation. In total, ADReCS-Target includes 66,573 pairwise relations, among which,70 are protein-adr associations, 2,63 are genetic variation-adr associations, and 63,298 are gene-adr associations. In a case study of exploring the mechanism of rash using ADReCS-Target, we find that HLAs, CQA and APOA are the key gene players and thus can be potential targets (or biomarkers) in monitoring or countermining rashes. In summary, ADReCS-Target can be a useful resource for the biomedical scientific community by serving researchers in the fields of drug development, clinical pharmacology, precision medicine, and from web lab to high-throughput computational platform. Particularly, it helps to identify drug with better ADR profile and design safer drug therapy regimen. Fig. Target profiles for ADR mechanism research under the ADR ontology framework. Keywords: Drug safety; Precision medicine; ADR ontology; ADR mechanism References: [] Cai, M; Xu, Q.; Pan, Y.; Pan, W.; Ji, N.; Li, Y.; Jin, H.; Liu, K.; Ji, Z.*. Nucleic Acids Res. 205, 43: D907-3. 59

I--8 OMICs based Target Discovery and Drug Binding Mode Identfication for Central Nervous System Disease Panpan Wang,2, Bo Li 2, Jing Tang 2, Weiwei Xue 2, Feng Zhu,2,* College of Pharmaceutical Sciences, University of Zhejiang, Hangzhou, 30058 2 School of Pharmaceutical Sciences, University of Chongqing, Chongqing, 4033 *Email: zhufeng@zju.edu.cn Metabolomics is tremendous increasingly being used to identify novel drug targets. In metabolite disease-association study, data processing and statistical analyses were two essential procedures for analysis of the complex metabolomics data generated. Although a variety of normalization methods have been developed, their performances vary greatly and depend heavily on the nature of the studied data. Herein, in order to address this problem, an online web server NOREVA was developed to enable performance evaluation of various normalization methods from multiple perspectives. Furthermore, finding metabolites disease-association required multivariate and univariate statistical analyses. The types of statistical analyses that can be implemented for identifying metabolites correlated to disease are vast, and choosing the correct statistical analysis approach can be of vital importance for those without a background in bioinformatics. Therefore, an additional online web server MMEASE was constructed to provide more comprehensive coverage and more user-friendly service in differential metabolite identification for metabolite disease-association study. After identification and validation of a novel drug target, computational chemistry method is an efficient strategy can be employed to understanding the drug interaction mechanism. Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed mental disorder of children and adolescents, which leads to serious problems in communication, emotion and career promotion. Till now, there are drugs for ADHD therapy exerted their therapeutic effects by targeting NET or/and DAT. However, targets residues capable of discriminating drugs addictiveness and selectiveness, and the way how different structures affected drugs properties were still elusive. This study integrated homology modeling, molecular docking, molecular dynamics (MD) and binding free energy calculation to differentiate binding modes between psychostimulants and drugs with little addictiveness, and between NDRIs and snris. As results, variations in energy contribution targets residues distinguish drugs addictive, non-addictive as well as selectivity were identified. The result might facilitate the discovery of improved ADHD therapeutics with reduced addictive profile and improved selectivity. Keywords: metabolomics; drug targets discovery; data normalization and statistical analyses; ADHD drug; molecular dynamics References: [] Wishart, D. S. C. Nat. Rev. Drug Discov. 206, 5: 473. [2] Li, B.; Tang, J.; Yang, Q.; Li, S.; Cui, X.; Li, Y.; Chen, Y.; Xue, W.; Li, X.; Zhu, F. Nucleic Acids Res. 207, doi: 0.093/nar/gkx449. [3] Li, B.; Tang, J.; Yang, Q.; Cui, X.; Li, S.; Chen, S.; Cao, Q.; Xue, W.; Chen, N.; Zhu, F. Sci. Rep. 206, 3888. [4] Global Burden of Disease Study, C. Lancet 205, 386: 743. [5] Maia, T. V.; Frank, M. J. Nat Neurosci 20, 4: 54. [6] Wang, P.; Zhang, X.; Fu, T.; Li, S.; Li, B.; Xue, W. * ; Yao, X.; Chen, Y.; Zhu, F. * ACS Chem. Neurosci. 207, 8: 46. 60

I--9 蛋白质磷酸化位点预测新方法研究 王雪, 李保琼, 翟红林 *, 刘金金, 卢韶华 兰州大学化学化工学院, 甘肃省兰州市,730000 *Email: zhaihl@lzu.edu.cn 蛋白质磷酸化是细胞内重要的调节机制, 磷酸化位点的有效辨识对生命活动研究有重要意义 磷酸化的发生需要满足特定的理化环境, 而磷酸化过程的可逆性对实验确认造成了一定的困难 ; 尽管磷酸化可发生于 S T Y 残基, 但并非所有的 S T Y 残基都属磷酸化位点, 现有的理论预测方法尚有改进的空间 基于对蛋白质序列片段进行理化属性数值化并结合 Krawtchouk 图像矩方法提取的有效特征信息, 我们提出了一种蛋白质磷酸化位点预测新方法 本研究采用拟南芥蛋白质磷酸化位点数据库中的样本, 借助氨基酸描述符对蛋白质序列片段数值化, 将获得的数值矩阵转换成灰度图后利用 Krawtchouk 矩提取局部特征信息, 并用于 SVM 建立预测模型 通过采用 0- 折交叉验证等多种统计分析和独立测试集对所建立的预测模型进行评价, 并与 4 个已有的预测工具做了对比 结果表明, 我们方法具有更好的准确性和可靠性 图. 几种预测工具对相同独立测试集样本预测的 ROC 曲线关键词 : 磷酸化位点 ; 预测 ;Krawtchouk 图像矩 ;SVM 建模参考文献 [] Kim, J.H.; Lee, J.; Oh, B.; Kimm, K.; Koh, I. Bioinformatics, 2004, 20(7): 379. [2] Aebersold, R.; Matthias, M. Nature, 2003, 422: 98. [3] Zhai, H.L. Expert Syst. Appl., 20, 38(6): 788. [4] Zhai, H.L.; Wang, X.H.; Huang, X.Y.; Shan, Z.J. Chemometr. Intell. Lab. Syst., 20, 07(2): 245. [5] Chen, J.; Li, B.Q.; Xu, M.L.; Wang, X.; Jing, Y. H.; Zhai, H.L. Talanta, 206, 6: 99. 6

I--20 Improving the Design of Non-interaction Pairs in Supervised Prediction of Drug-Target Interactions Ming-Yang Tu, Chao Chen *, Xiao-Yong Zou 2 School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 50006, PR China 2 School of Chemistry, Sun Yat-sen University, Guangzhou 50275, PR China E-mail: gdpuchenchao@63.com (C. Chen). In genomic drug discovery identification of drug-target interactions is one of the most important research tasks, and it is of great importance to construct in silico predictors for accurate identification of drug-target interactions. In construction of a binary classification model, non-interaction pairs are often needed, and taken as the negatives in the training-set. However, very few information about them are available yet. In practice, the putative negatives are usually randomly selected non-interacting drug-target pairs in which none of them occurs in the known positives. However, these unconfirmed negative pairs may contain the potential interactions, thus bringing noise to the experiments and hindering the model accuracy. In order to deal with the challenge, here we proposed a computational strategy for more reasonably constructing the non-interaction pairs, i.e., firstly to cluster the drugs or targets into certain families by k-means clustering of their molecular descriptors or protein representations, and secondly, to extract the putative non-interaction pairs in those families without a single known pair. As shown in Fig., the unknown pairs in the diamond rather than oval regions were selected as the putative non-interactions. In the top left corner, pair a prior to pair b was selected as a better putative due to the shorter distance to the clustering center. Using machine learning methods, including random forests, support vector machines and k-nearest neighbors, the predictive qualities were evaluated on four benchmark datasets by 0-fold cross validation tests. The predicted non-known interactions were verified by Drug2Gene, and some typical pairs were analyzed in detail. The results yielded were much satisfying, thereby confirming the validity of our approach. Fig. Scheme of the present 2-step strategy for negatives construction Keywords: drug-target interaction; non-interaction pair; machine learning; prediction References: [] Yamanishi Y, Araki M, Gutteridge A, et al. Bioinformatics 2008, 24: i232. [2] Coelho E D, Arrais J P, Oliveira J L. PLoS Comput Biol, 206, 2: e00529. [3] Wen M, Zhang Z, Niu S, et al. J Proteome Res, 207, 6: 40. 62

I--2 Identification and validation of novel kinase allosteric sites 张健上海交通大学 63

I--22 New Strategy for Prostate Cancer Yong XU Guangdong Provincial Key Laboratory of Biocomputing, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, No. 90 Kaiyuan Avenue, Guangzhou, Guangdong 50530, China. Email: xu_yong@gibh.ac.cn Prostate cancer (PCa) is the most common cancer in men and remains the second leading cause of cancer mortality in men. [-3] Androgen-deprivation therapy (ADT) represents the gold standard treatment for PCa. However, disease will inevitably recur and progress to a lethal form named castration-resistant prostate cancer (CRPC). CRPC remains androgen receptor (AR) signaling dependent and responds to recently approved androgen-signaling inhibitor enzalutamide and the androgen-synthesis inhibitor abiraterone acetate. Most patients eventually develop resistance to these second-generation therapies as well. Therefore, alternative strategy for development of next generation therapeutic agents is urgent needed. Here, we will present the identification and validation of new therapeutic targets for CRPC. By combining computational biology, computer-aided drug design with chemical biology and structural biology, some epigenetic proteins were identified as targets for CRPC. As case studies, development of BRD4 and CBP inhibitors against CRPC will be presented. Key words: Prostate cancer, CRPC, Nuclear receptor, Bromodomain References [] Wang, J.; Zou, J. X.; Xue, X.; Cai, D.; Zhang, Y.; Duan, Z.; Xiang, Q.; Yang, J. C.; Louie, M. C.; Borowsky, A. D.; Gao, A. C.; Evans, C. P.; Lam, K. S.; Xu, J.; Kung, H. J.; Evans, R. M.; Xu, Y.*; Chen, H. W*. ROR-gamma drives androgen receptor expression and represents a therapeutic target in castration-resistant prostate cancer. Nat Med, 206, (22): 488-496. [2] Siegel, R.; Ma, J.; Zou, Z.; Jemal, A. Cancer statistics, 204. CA Cancer J. Clin. 204, (64), 9-29. [3] Ferlay, J.; Steliarova-Foucher, E.; Lortet-Tieulent, J.; Rosso, S.; Coebergh, J. W.; Comber, H.; Forman, D.; Bray, F. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 202. Eur. J. Cancer 203, (49), 374-403. 64

I--23 K2P 通道动态构象多位点药物设计 阳怀宇 华东师范大学生命科学学院, 上海市闵行区东川路 500 号,20024 Email: hyyang@bio.ecnu.edu.cn 抑郁 疼痛 中风等神经系统疾病的临床治疗急需靶向新靶标的首创药物 基因敲除等生物学研究结果已表明双控钾离子 (K2P) 通道中的一些成员是抑郁 疼痛 中风等疾病的潜在药靶 通过膜片钳等实验方法发现这些通道的活性小分子较困难 我们研究了 K2P 通道的动态构象, 提出了抑制和激活通道的策略, 以此为基础通过药物设计方法获得了一批 K2P 通道的抑制剂和激动剂 在小鼠体内实验中, 与基因敲出等生物学研究结果一致, 这些分子表现出了治疗相关神经系统疾病的药效 关键词 : 双孔钾通道 ;K2P; 抑郁 ; 疼痛 ; 中风参考文献 [] Luo, Q.; Chen, L.; Cheng, X.; Ma, Y.; Li, X.; Zhang, B.; Li, L.; Zhang, S.; Guo, F.; Li, Y.; Yang, H. An allosteric ligand-binding site in the extracellular cap of K2P channels. Nat. Commun. (In press). 65

I--24 以信息化和人工智能建立基于化学结构的大数据 邓光辉 上海鹰谷信息科技有限公司 66

I--25 Prediction of protein protein interaction using a deep-learning algorithm 裴剑锋 Abstract: Protein-protein interactions (PPIs) are critical for many biological processes. It is therefore important to develop accurate high-throughput methods for identifying PPI to better understand protein function, disease occurrence, and therapy design. Though various computational methods for predicting PPI have been developed, their robustness for prediction with external datasets is unknown. Deep-learning algorithms have achieved successful results in diverse areas, but their effectiveness for PPI prediction has not been tested.we used a stacked autoencoder, a type of deep-learning algorithm, to study the sequence-based PPI prediction. The best model (http://repharma.pku.edu.cn/ppi) achieved an average accuracy of 97.9% with 0-fold cross-validation. The prediction accuracies for various external datasets ranged from 87.99% to 99.2%, which are superior to those achieved with previous methods.to our knowledge, this research is the first to apply a deep-learning algorithm to sequence-based PPI prediction, and the results demonstrate its potential in this field. 67

I--26 呈现蛋白质构象转变的插值旋转优化方法 刘权, 钟世钧 * 大连理工大学生命科学与技术学院, 辽宁省大连市甘井子区凌工路 2 号, 邮编 6024 *Email: sjzhong@dlut.edu.cn 蛋白质与其它分子的作用会引起局部构象的明显改变, 包括 loop 翻动 活性位开合等 在这样的构象变化过程中, 不只是关键位置在转变, 整个蛋白质的构象也在调整 而且, 较大的侧基还会出现取向相反的翻转 这为模拟构象变化过程增大了复杂程度 我们最初尝试了几个简单方法 : 直接的插值不能产生合理的初始结构, 也很难进行优化 ; 施用侧基取向翻转的旋转矩阵能够处理环平面取向, 但是还欠缺整体合理构象 ; 添加类似于 umbrella sampling 的限制, 可以进一步维持侧基合理结构 于是, 我们得到一种组合方法 插值 - 旋转 - 限制 - 优化 来实现这种复杂的构象转变 关键词 : 蛋白质构象转变 ; 插值方法 ; 旋转矩阵 ; 限制性优化参考文献 [] Case D A, Cheatham T E, Darden T, et al. J comput chem, 2005, 26(6): 668. [2] Goossens K V Y, Ielasi F S, Nookaew I, et al. Mbio, 205, 6(2): e00427-5. [3] Kobayashi O, Hayashi N, Kuroki R, et al. J bacteriology, 998, 80(24): 6503. [4] Bidard F, Bony M, Blondin B, et al. Yeast, 995, (9): 809. 68

I-2-0 高维化学计量学方法用于温控近红外光谱数据分析 崔晓宇, 程丹, 朱雪薇, 马丽, 王丽, 蔡文生, 邵学广 * 南开大学化学学院, 分析科学研究中心, 天津,30007 *Email: xshao@nankai.edu.cn 温度变化会导致分子内或分子间相互作用发生变化, 因此近红外 (NIR) 光谱容易受到温度的影响, 通常称为温度效应 通过程序升温法采集不同温度下的近红外光谱, 发展了温控近红外光谱技术 温控近红外光谱数据中不仅包含了样品本身的物理化学信息, 还包含了在温度扰动下样品分子分子内或分子间相互作信息 但是, 温控 NIR 光谱数据一般是二维 三维甚至更高维的数据矩阵 由于数据维数的增加, 传统的化学计量学算无法建立有效模型完整的描述光谱数据中的有效信息 因此, 需要高阶的化学计量学方法对温控近红外光谱数据进行解析 本课题组利用温控近红外光谱技术在定量分析和结构分析两方面开展了研究工作 首先使用偏最小二乘 (PLS) 模型建立了光谱 - 温度定量模型 ( 称为 QSTR 模型 ), 并在此基础上发展了一种预测溶液组成的定量分 [,2] [3] [4] 析方法 随后, 使用多级同时成分分析 (MSCA) 方法, 对多组分样品中的异丙醇和血清中的葡萄糖进行了定量分析 同时, 还使用交替三线性分解 (ATLD) 的方法解析混合烷烃的温控近红外光谱数据, 得到了 [5] 直链烷烃中两种 CH 基团的特征光谱, 并根据两者的相对含量变化建立了直链烷烃混合物的定量分析模型 使用 MSCA 分析葡萄糖水溶液的温控近红外光谱, 从中提取出不同结构的水的特征光谱, 解释了葡萄糖在溶 [4] 液中的生物保护作用 还采用多维主成分分析 (NPCA) 平行因子分析 (PARAFAC) 和 ATLD 等三种高阶算法, 分别从不同温度下酒精水溶液的光谱数据中提取信息, 研究了水和乙醇相互作用 关键词 : 温控近红外光谱技术 ; 高阶化学计量学算法 ; 定量信息 ; 结构信息参考文献 [] Shao, X.G.; Kang, J.; Cai, W.S. Talanta 200, 82: 07. [2] Kang, J.; Cai, W.S.; Shao, X.G. Talanta 20, 85: 420. [3] Shan, R.F.; Zhao, Y.; Fan, M. L.; Liu, X.W.; Cai, W.S.; Shao, X.G. Talanta 205, 3: 70. [4] Cui, X.Y.; Liu, X.W.; Yu, X.M.; Cai, W.S.; Shao, X.G. Anal. Chim. Acta 207, 957: 47. [5] Qi, L.H.; Cai, W.S.; Shao, X.G. Acta Chim. Sinica 206, 74: 72. 国家自然科学基金项目 (No. 2475068) 资助 69

I-2-02 采样误差分布分析 (SEPA) 及其在近红外光谱分析中的应用 杜一平 *, 陈万超, 张飞宇 华东理工大学上海市功能性材料化学重点实验室, 化学与分子工程学院, 上海市梅陇路 30 号,200237 *Email: yipingdu@ecust.edu.cn 在近红外光谱分析中, 为了建立稳健模型经常采取 Monte Carlo 采样方法对数据进行分配集合 采用单次采样以及多次采样后取平均方法都有一些参数需要事先优化, 所获得的模型也不一定稳健 本文提出采样误差分布分析 (Sampling Error Profile Analysis, SEPA) 方法, 对 Monte Carlo 采样获得的多个集合数据分别进行建模, 再对所有子模型进行误差分布分析, 进而获得误差的中位数 方差, 以及误差分布的峰度 (Kurtosis) 和偏度 (Skewness) 峰度和偏度有利于判断误差分布的合理性, 可用于辅助判断模型的优劣, 用中位数代替平均值估计模型误差则更加稳健, 而误差的方差是对误差估计值变化范围的估计, 结合中位数可更全面地对模型进行评价 SEPA 方法可用于异常点筛选 光谱预处理方法优化 波长选择 交互检验, 以及对模型的全面评价 本文采用三套近红外光谱分析数据对所提算法 SEPA 进行性能评估, 并与常见建模方法做了比较, 结果发现,SEPA 可以获得更优异的优化参数, 对模型的评价指标更合理 图 SEPA 工作流程关键词 : 采样误差分布分析 ; 条件优化 ; 建模 ; 近红外光谱参考文献 []Chen, W.; Du, Y.; Zhang, F.; et al. J. Chemometr. 207, e2933. https://doi.org/0.002/cem.2933 70

I-2-03 The Application of Data Driven Raman Spectroscopy in Oil and Gas Exploration Inudstry Xi Han, Zhixuan Huang, Qifeng Li, Da Chen * College of Precision Instrument and Opto-Electronics Engineering, Tianjin University, Tianjin 300072 *Email: dachen@tju.edu.cn Mud logging system presents the most promising tool for exploring oil and gas resources, which relies on the multi-component analysis of gases to evaluate the hydrocarbon reservoirs. Higher detection efficiency, especially relating to the high-throughput analysis, can offer an important means to enhance the oil and gas recovery of hydrocarbon reservoirs. However, fewer technologies can measure both hydrocarbon and non-hydrocarbon gases in a timely manner []. In the present work, a method based on data driven Raman spectroscopy (DDRS), which allows simultaneously accurate analysis of 2 hydrocarbon and non-hydrocarbon gases, has been proved. The DDRS provides an excellent chemical selectivity that allows the identification of almost all hydrocarbon and non-hydrocarbon gases (except noble gases). With the combination of the Raman spectroscopy hardware and the DDRS method, a novel Raman gas analysis system was thus designed based on a portable spectrometer following the industrial standards. We have validated the Raman systems by means of systematic analysis of 2 gas components in the standard gas samples, together with methane analysis in the two realistic gas logging data sets. The DDRS compared favorably with the gas chromatography (GC) method. The satisfactory results indicated that the DDRS has the capability to continuously detect 2 hydrocarbon and non-hydrocarbon gases in real time. The Raman system can be also applied to the on-line monitoring of other various gases for quantitative purposes as well. Fig. Multi-component analysis of gases obtained by the DDRS Keywords: oil and gas exploration; data driven Raman spectroscopy; Higher-density discrete wavelet transform; gas ensing References: [] Khoshbakht, F.; Rasaie, M.R.; Shekarifard, A. J. Pet. Sci. Eng. 206, 45: 357. [2]Yan, F.; Cheng, L.; Wang, H. IET. Signal. Process. 2007, : 64-69. 7

I-2-04 数据挖掘辅助材料设计研究进展 陆文聪 *, 张庆 2, 卢凯亮 2, 纪晓波 上海大学理学院化学系,200444 2 上海大学材料科学与工程学院,200444 *Email: wclu@shu.edu.cn 本文报导数据挖掘辅助材料设计研究进展, 通过具体研究案例介绍材料数据挖掘方法和过程. 数据挖掘方法 ( 或机器学习方法 ) 包括定性方法和定量方法, 分别用以建立定性模型或定量模型 不同的数据挖掘方法适用于材料设计各种不同的目的, 包括新材料发现和性能优化等 本文重点讨论了树枝状 Co3O4 材料的模式识别和控制合成 层状双金属氢氧化物层间距的预报和控制合成等材料设计问题 有关工作表明 : 材料数据挖掘方法是材料设计和优化的有力工具, 有望在全球材料基因组工程研究和材料信息学研究工作中发挥重要作用 : dendritic Co3O4 superstructures; : non Co3O4 superstructures; : Samples designed and predicted to be dendritic Co3O4 superstructures Fig. Classification diagram of pattern recognition using OPR method 关键词 : 数据挖掘 ; 材料设计 ; 化学信息学 ; 材料信息学参考文献 [] Zhang Qin, Zhai Xiu-yun, Xiong Pan, Kou Li, Ji Xiao-bo, Lu Wen-cong, Mater. Res. Bull. 207, 93, 23-29. [2] Lu Wen-cong, Ji Xiao-bo, Li Min-jie, Liu Liang, Yue Bao-hua, Zhang, Liang-miao, Adv. in Manuf. 203, (2), 5-59. [3] Wu Mi-lin, Zhang Liang-miao, Gu Tian-hong, Qian Na, Ma Wen-Jing, Lu Wen-cong, Adv. Mater. Res. 203, 652-654, 352-355. 72

I-2-05 基于多领域数据信息融合的化合物致癌性预测 阎爱侠 *, 孔越 北京化工大学化工资源有效利用国家重点实验室, 生命科学与技术学院, 北京市朝阳区北三环东路 5 号,00029 *Email: yanax@mail.buct.edu.cn 化合物的致癌性与人类健康和环境安全息息相关, 致癌性计算预测模型的建立可以帮助人类高效准确地排查致癌物 而随着化学信息学和生物信息学等学科的不断发展壮大, 相关的科学实验数据信息实现了规模化 系统化 共享化 本课题探究能否通过融合多学科领域数据信息的方法, 来提高化合物致癌性预测模型的性能 本课题建立了一个包含 26 个化合物致癌性信息的数据集, 计算或收集化合物的结构特征 物理化学性质 蛋白靶点信息 致突变性和毒性通路高通量筛选测试结果等多领域信息, 构建化合物的多维描述符, 分别采用四种机器学习方法 ( 朴素贝叶斯 随机森林 多层感知机和支持向量机 ), 各建立了 00 个致癌性分类预测模型 研究表明, 多领域数据信息的融合提高了模型的预测准确率, 结合结构特征 物理化学性质和蛋白靶点信息这三个领域的信息比使用单一领域信息的建模效果好,00 个模型的平均正确率达到 74% ± 3%; 致突变性信息的加入可普遍提高致癌性模型的正确率 ;Toxcast 项目的毒性通路高通量筛选测试结果并不能显著提高模型的正确率, 其数据使用和融合方式有待进一步探究 另外, 通过对四种机器学习方法在致癌性模型性能上的比较, 随机森林和支持向量机的表现较为突出, 性能优于朴素贝叶斯和多层感知机 关键词 : 化合物致癌性预测 ; 随机森林 ; 支持向量机 73

I-2-06 激光诱导击穿光谱中的化学计量学理论与方法研究 李华,2,*, 张天龙, 汤宏胜 西北大学化学与材料科学学院分析科学研究所, 陕西, 西安,70069 2 西安石油大学化学化工学院, 陕西, 西安,70065 *Email: huali@nwu.edu.cn 激光诱导击穿光谱技术 ( 简称 LIBS) 是一种基于原子发射光谱且激光作为激发源的新兴物质元素分析技术, 相比传统的分析技术, 该技术具有快速 实时在线分析 无需复杂样品前处理 多元素同时分析以及远程探测等优势, 因而在工业过程分析与控制 食品药品监督 环境监测 科技考古 太空探测等关键领域得到了广泛应用 然而, 如何从复杂大量的激光诱导击穿光谱数据提取有用信息, 提高其定性 定量分析准确度已成 LIBS 技术发展的一个瓶颈问题和主要研究方向 近年来, 本实验室发展了系列性能优良, 易于实现的研究现场和在线 LIBS 分析的化学计量学新算法, 实现少标样或无标样的自由定标分析, 并将各种可用于 LIBS 光谱预处理及光谱分析的化学计量学方法进行集成, 进一步提高了 LIBS 现场测量及其他分析应用中的可行性与可靠性 基于所建立的现场 LIBS 分析的化学计量学理论和方法, 有望进一步丰富现场分析技术, 为现场分析提供先进的分析手段, 并有助于提高我国在科学仪器研究源头的创新能力 ; 该成果将有望在石油 冶金 地质 环保 军事 航天等领域及相关行业的实际应用中取得具有自主知识产权的原创性技术成果 ; 引领世界现场分析仪器的发展方向, 并为建立战略性新兴产业奠定基础 关键词 : 激光诱导击穿光谱 ; 化学计量学 ; 自由定标法 ; 参考文献 [] Fortes F. J.; Moros J.; Lucena P.; Cabalín L. M.; Laserna J. J.; Anal. Chem., 202, 85: 640. [2] Cremers D. A.; Radziemski L. J.; Wilkey & Sons Ltd Press, 2006:. [3] Zhang T.; Wu S.; Tang H.; Wang K.; Duan Y.; Li H.; Chin. J. Anal. Chem., 205, 43(6): 939. [4] Wang Z.; Yan C.; Dong J.; Zhang T.; Wei J.; Li H.; RSC Advances, 206, 6(80): 7683. [5] Zhang T.; Xia D.; Tang H.; Yang X.; Li H.; Chemometr. Intell. Lab., 206, 57: 96. [6] Yan C.; Qi J.; Ma J.; Tang H.; Zhang T.; Li H.; Chemometr. Intell. Lab., 207,67: 226. 本工作得到了科技部重大仪器设备开发专项 (No. 20YQ0303) 和国家自然科学基金 (No. 237505, 260523) 的支持 74

I-2-07 Mathematization of Quantitative Analysis Feng Gan *,Yong Li,Weilan Yang,Lianyun Li School of Chemistry,Sun Yat-Sen Univeristy,Guangzhou,50275 *Email: cesgf@mail.sysu.edu.cn The aim of this work is to establish a mathematical theory for chemical quantitative analysis and then to fuse it with instrumental analysis technique and chemometrics to construct new absolute quantitative analysis method. We established concentration models to calculate the concentration profiles of the species in the reaction between an analyte and a reagent. We set up signal models to connect the concentration profiles of the species with their measured signal intensities, which construct two-way or three-way data array naturally depending on the analytical instruments used. Chemometrics methods were introduced to extract the concentration profiles of the species with measurable responses from the data array. We found that there is a maximum point on the concentration profile of some reaction products and it can be used to calculate the concentration of the analyte directly. A mathematical proof was provided to confirm our findings for a simple reaction system but the conclusions are extensible to relatively complicated system. Several examples were also provided to show the validity of the theory. The approach could throw a new light upon the mathematization of quantitative analysis. 关键词 :Quantitative analysis;mathematization;chemometrics 参考文献 [] Kant, I.; Bax, E. B. The Metaphysical Foundation of Natural Science, Createspace Independent Publishing Platform, 205. [2] Dirac, P.A.M. Proc. R. Soc. London, Ser. A 929,23:74. [3] Karayannis, M.I.; Efstathiou, C.E. Talanta. 202, 02:7. 75

I-2-08 化学计量学在食品质量控制和食品安全机理研究中的应用 郭瑛, 张秋兰, 王勇 2, 倪永年,* 南昌大学食品科学与技术国家重点实验室, 南昌, 330047 2 南昌大学化学学院, 南昌, 33003 *Email: ynni@ncu.edu.cn 食品是人类赖以生存和发展的物质基础, 食品安全问题关系到人体健康和国计民生的重大问题 由于食品在生产 加工和储存过程中, 可能会受到多种有毒物质的污染, 如农药残留 兽药残留和有害添加剂等, 使得食品的品质受到很大的影响 加强食品中有害物质的快速和有效的监测, 对保障食品的安全 促进人类健康及社会经济发展都具有重大的现实意义 传统的方法是选择性分析一些标志性化合物来进行质量控制, 这并不能反映食品和中药这类复杂物质的全部信息, 同时不能全面考虑到化合物之间的协同配伍作用, 而指纹图谱技术具有整体性和模糊性的特点, 能够较全面地反映复杂物质多种化合物的内在作用关系并显示特定的化学模式特点, 通过与模式识别技术相结合可有效地提取分析有用信息 同时由于食品分析体系往往比较复杂, 仪器测量所得波谱往往比较复杂且重叠, 因此采用化学计量学方法来解析波谱指纹图谱也是非常重要, 可以通过分析仪器获取多维数据信息, 然后用化学计量学如多元曲线 - 交替最小二乘法和平行因子分析法等来处理这些包含较多信息的数据, 从而得到使用普通方法不能得到的信息, 有助于食品复杂体系的深入研究 利用指纹图谱可以鉴别真伪 控制产品质量的稳定性 保证食品的营养功效具有一定的现实指导意义 化学计量学在食品分析中的应用, 为食品的分析注入了新鲜的血液, 不同程度的解决了农药残留检测以及现代仪器数据和食品分析中分别面临的多组分分析问题和仪器数据复杂化 多维化的问题 对化学计量学在食品分析中的研究本实验室早期的工作主要是对食品有害元素 农药残留检测检测以及在掺伪分析 分类识别等方面的应用进行研究 化学计量学在研究生命过程和生物医学中都有比较重要的意义, 在很多有关生命科学的研究规划中, 化学计量学都发挥了重要作用 生物大分子是生物体的重要组成成份, 包括蛋白质 核酸和碳氢化合物等, 它们在体内的运动和变化体现着重要的生命功能, 如进行新陈代谢供给维持生命需要的能量与物质 传递遗传信息 控制胚胎分化 促进生长发育 产生免疫功能等等 化学计量学在蛋白质研究中应用得比较多, 特别是蛋白质的结构研究, 并且也取得了一定的成果 总之, 化学计量学在研究生命过程和食品安全检测都有比较重要的使用意义, 在很多有关生命科学的研究中, 化学计量学都发挥了重要作用. 而化学计量学近年来发展的强劲势头, 对分析化学在新世纪科学进步中发挥更为重要的作用提出了新的要求和挑战 分析化学和生命科学已密不可分, 有理由相信, 化学计量学在生命科学研究中应用的迅速发展, 将会推动生命科学和食品安全的又一次飞跃和革命 关键词 : 食品安全 ; 食品质量 ; 生命科学 ; 参考文献 [] Zhang, Q.L.; Ni, Y.N. RSC Adv. 207, 7, 39833-3984 [2] Zhang, Q.L.; Ni, Y.N; Kokot, S. Analyst 206, 4: 228-2227. [3] Guo, Y.; Ni, Y.N.; Chen, J.F.; Kokot, S. Anal. Methods 206, 8, 97 204. [4] Wang, Y.; Chen, T.X.; Zhuang, Q.F.; Ni. Y.N. ACS Appl. Mater. & Inter. 207 (in press) 76

I-2-09 网络方法在肿瘤基因分析和靶标蛋白研究中的应用 卞希慧 天津工业大学 77

I-2-0 机器学习在化学与生物学中的应用漫谈 李梦龙 四川大学 78

I-2- 基于深度学习的蛋白质相互作用预测方法 邹小勇 *, 王洋, 李占潮 2, 戴宗. 中山大学化学学院, 广州,50275 2. 广东药科大学医药化工学院, 广州, 50240 *ceszxy@mail.sysu.edu.cn 蛋白质相互作用关系不仅直接影响到细胞接收外源和内源信号, 还参与调节基因的表达, 以及介导和调控细胞的生物学活性, 因此, 蛋白质相互作用的研究具有十分重要的生物学意义 但是该研究受蛋白质序列 蛋白质复合物和环境条件等诸多因素影响, 对分析模型的复杂性和性能要求较高 深度学习方法源于人工神经网络, 通过建立多隐藏层的结构实现对蛋白质数据的多特征提取和处理, 在蛋白质数据分析上 [-5] 具有明显的优势, 并取得了优异的成果 本文基于深度学习思想设计卷积神经网络模型, 使用蛋白质大数据训练和优化模型参数, 建立蛋白质相互作用的机器学习方法, 以及预测潜在的蛋白质相互作用关系 结果表明, 本方法的准确率为 89.93%, 敏感度为 89.26%, 特异性为 90.43%, 精确度为 89.80%, 马氏相关系数为 0.7968 与现有方法相比较, 本方法不但表现出更加良好的性能, 还可以根据蛋白质数据特征的不同提取方法进行其他功能拓展性研究 同时, 基于卷积神经网络模型迁移学习技术可以保证本方法快速有效地应用于蛋白质相关领域的其他研究 训练集测试集校验集两层卷积操作采样处理两层卷积操作采样处理中间过程计算处理 经验模型 约束处理 dropout 优 训练分类 分类 输出 (a) (b) (c) 图 (a) 卷积神经网络流程图 ;(b) 不同卷积核数对模型性能影响 ;(c) 迭代训练程度对模型性能的影响 关键词 : 蛋白质相互作用分析 ; 卷积神经网络 ; 数据增维方法参考文献 [] Alipanahi B, Delong A, Weirauch M T, et al. Predicting the sequence specificities of DNA-and RNA-binding proteins by deep learning[j]. Nature biotechnology, 205, 33(8): 83-838. [2] Fowler D M, Fields S. Deep mutational scanning: a new style of protein science[j]. Nature methods, 204, (8): 80-807. [3] Zeng H, Edwards M D, Liu G, et al. Convolutional neural network architectures for predicting DNA protein binding[j]. Bioinformatics, 206, 32(2): i2-i27. [4] Wang S, Ma J, Xu J. AUCpreD: proteome-level protein disorder prediction by AUC-maximized deep convolutional neural fields[j]. Bioinformatics, 206, 32(7): i672-i679. [5] Jiménez J, Doerr S, Martínez-Rosell G, et al. DeepSite: Protein binding site predictor using 3D-convolutional neural networks[j]. Bioinformatics, 207. 本文系国家自然科学基金资助项目 (267580,2675035) 79

I-2-2 酶分子催化机制 : 预反应态决定底物选择性? * 赵一雷 上海交通大学生命科学技术学院微生物代谢国家重点实验室, 上海市东川路 800 号,200240 *Email: yileizhao@sjtu.edu.cn 随着基因编辑技术的快速发展, 在抗生素工业合成上微生物生物合成已经与传统的有机化学合成方法并驾齐驱 通过定性进化等现代酶工程方法能够快速突变关键基因的特定碱基及其编码功能蛋白, 从而高效地提高生物合成中目标代谢产物的产量和纯度 然而, 由于酶分子体系量子力学理论计算的复杂性, 人们对其微观分子机制的了解程度远落后于蛋白质工程的实验效率 我们提出利用经典分子动力学模拟结合反应途径分析的方法, 通过定性计算不同底物预反应态的占比来预测突变对底物选择性的影响 我们将通过对 PKS 生物合成酶系硫酯酶作为例子来说明预反应态 :PKS 酶系合成了医学应用非常广泛的多种大环内酯类药物, 在其模块化的合成机制中硫酯酶是决定目标产物环化释放的关键酶 [] 我们利用两个结构极为相近的底物分子探索红霉素 DEBS 生物合成酶系中硫酯酶的环化和水解反应的竞争机制 [2] 通过对 SNAC 化底物上载后的酶 - 底物共价复合物的经典分子动力学模拟, 结果表明了酶与底物之间的诱导契合过程决定了不同底物对反应途径的竞争优势 : 共价结合底物的末端羟基与活性中心三联体组氨酸之间的氢键相互作用, 以及 Lid 区的变构效应构成了疏水口袋是催化环化反应进行的关键因素 预反应态的形成需要克服.6 kcal/mol 的酶 - 底物复合物的结构变化势垒, 而形成内酯化学键反应的势垒仅 9.9 kcal/mol; 如果没有形成特定环化构象 (pre-organization) 将直接被水解释放而产生线性产物 Fig. The proposed pre-reaction state, by which the bifurcated pathways are determined. 关键词 : 生物合成, 过渡态, 预反应态, 硫酯酶参考文献 [] Khosla C., Tang Y., Chen A. Y., et al., Annu. Rev. Biochem. 2007, 76: 95 22. [2] Chen X.-P., Shi T., Wang X.-L., et al. ACS Cat., 206, 6, 4369-4378. 80

I-2-3 蛋白核酸相互作用的理论模拟 李根, 杜利凯, 别丽华, 高军 *, 农业生物信息湖北省重点实验室, 华中农业大学信息学院, 湖北省武汉市洪山区狮子山街 号,430070 *Email: gaojun@mail.hzau.edu.cn 蛋白核酸相互作用在基因的表达和调控中发挥着重要作用 在真核生物中, 转录因子可特异性结合 DNA 序列, 精确调控遗传信息的转录过程, 与细胞的代谢 周期 分化及死亡等各个过程密切相关 转录因子与 DNA 结合过程涉及到蛋白核酸相互作用 蛋白蛋白相互作用 残基突变及单核酸多态性等诸多因素 目前我们对这些因素组合调控转录因子的特异性结合的分子机制还知之甚少 分子动力学模拟方法和生物信息学方法的有机结合可在蛋白核酸相互作用的理论模拟方面发挥重要作用 我们采用分子动力学模拟方法, 并结合生物信息学统计信息, 从蛋白蛋白相互作用 单核酸多态性等方面探讨了转录因子组合调控的分子机制 研究表明,BZIP 家族中转录因子二聚体间因残基突变导致的蛋白蛋白相互作用减弱可诱导并增强蛋白核酸相互作用, 从而导致转录因子对特异序列的选择性增强, 这一结论与实验观察和生物信息学分析结果一致 ; 单核酸多态性可导致 DNA 大沟和小沟的宽度和深度发生变化, 通过构象传递影响附近的碱基对构象, 从而影响转录因子的结合强度, 导致基因的上调和下调 根据这些研究成果, 我们还进一步构建了 3-mer DNA 碱基堆积矩阵 统计分析表明, 这一矩阵与单核苷酸多态性 (SNPs) 是否具有致病倾向存在强关联, 可用于进行致病性 SNP 位点和蛋白核酸相互作用位点的筛选和预测 同时, 课题组也采用拉伸动力学方法对蛋白核酸相互作用的动态机制进行了系统研究 这些研究成果对于揭示转录因子组合调控机制, 理解转录调控过程具有积极意义 Fig. Structure of the GCN4 bzip homodimer binding to DNA. 关键词 : 转录因子 ; 单核酸多态性 ; 分子动力学模拟 ; 分子机制 This work is supported by the National Natural Science Foundation of China (No. 237324) 8

I-2-4 化学计量学在现代光谱过程分析技术中的应用研究 袁洪福, 朱志强, 宋春风 *, 谢锦春, 孙禧亭, 李效玉 北京化工大学材料科学与工程学院, 邮编 00029 *Email: yhf204@26.com 物质组成与结构决定着其属性, 光谱是物质属性之一 当组成发生改变, 其光谱也随之改变 光谱通 过组成的内因与待测性质存在着相关函数关系, 其中, 是光谱向量, 是待测性质 随着科 学仪器技术发展, 使得的测量变得很容易 通过建立相关函数关系, 可实现被测性质 ( 组成与物化 性质 ) 的快速 无损和高通量分析, 用于过程分析可显著降低生产成本和保证产品质量, 对于提高企业市 场竞争能力具有积极作用 用于现场检测, 实现监管流通领域中商品质量, 对社会治理具有重要的促进作 用 因此, 光谱过程分析技术的发展得到了工农业生产和质量监管等领域方面的高度关注 在光谱过程分析技术中, 是核心技术之一, 它的建立离不开光谱分析理论基础, 即朗姆伯特比尔 定律 但是, 过程分析中的样品不仅形态变化很大, 而且组成也很复杂 得到光谱信号除包含对待测性质 有用的化学信息外, 还包括共存组分信息的干扰, 还有来自样品形态和环境变化等因素产生的噪声 传统 光谱分析使用单个波长 ( 单变量 ) 建立工作曲线的方法不再适用 化学计量学方法在消除共存信息的干扰 方面表现卓越, 已经成为建立 的主要技术, 在现代过程分析技术中具有不可替代作用 本文旨在介绍作者研究团队关于化学计量学在现代光谱过程分析技术中的典型应用研究, 涉及领域包 括现代农业 石油化工 纺织 交通和食品安全等 关键词 : 化学计量学 ; 光谱 ; 过程分析 ; 参考文献 [] Zhang, S.; Li, S.; Zhou, W.; Zheng, L. Chem. Phys. 20, 35: 4304. [2] 作者一, 作者二, 作者三, 作者四. 杂志名称, 200, 26(4): 05 82

I-2-5 多元谱学新方法在食药质控中应用 付海燕,*, 范尧, 尹桥波, 刘丽, 杨天鸣 中南民族大学, 湖北省武汉市洪山区民族大道 82 号,430074 *Email: fuhaiyan@mail.scuec.edu.cn; 民以食为天, 食以安为先, 食药安全是关系到国计民生的重大问题, 食药安全分析的核心任务即是通过对反映食药特征品质 ( 如其营养活性成分 外源的农药兽药残留 非法添加的违禁物质 内源的霉菌毒素等指标, 以及食药分级分类 掺伪假冒等 ) 的量测数据性质和信息进行甄别和定性定量分析, 进而为评判 [] 食药质量好坏和食用安全性提供依据, 而保证食药安全和品质的有效手段之一就是建立简单 快速 准确的新型谱学方法 然而, 由于食药种类繁多 成分复杂类似, 从而导致其谱学性质也极为相似 因此, 需借助化学计量学方法对隐含于复杂谱学数据中的大量化学信息差异进行提取和分析, 通过建立一类或多类 [2-4] 模式识别模型, 达到对不同特征类别食药品质快速判别的目的 但对于解决严重的类重叠和低分辨率数 [5] 据的食药复杂体系大类数精细分类问题时, 则对传统谱学分析方法提出了新的挑战 最近, 我们基于纳米材料具有量子尺寸效应 场效应 表面效应等性质, 通过利用其纳米信号放大功能和光电性能, 应用在食药复杂体系中展现出了优秀的分子识别能力, 从而通过运用化学计量学结合纳米效应多元光谱新方法实现 [6] 了多种不同品质茶叶的大类数精细分类, 以及在多种中药材和茶叶等复杂基质中多组分农残的高灵敏定量 [7] 检测分析 因此, 我们所建立的纳米效应多元谱学新方法可为食药质控分析提供一种新的途径 Fig. Illustration of problems in quality control of food and Chinese medicinal materials 关键词 : 化学计量学 ; 谱学技术 ; 纳米效应 ; 食药品质分析 参考文献 [] Dzantiev, B.; Byzova, N.; Urusov,A.; Zherdev, V. Trac. Trend. Anal. Chem. 204, 55: 8. [2] Fu,H., Li, H.; Xu, L.; Yin, Q.; Yang, T.; Ni, C.; Cai, C.; Yang, Ji.; She,Y. Food Chem. 207, 227:322. [3] Fu,H., Yin, Q.; Xu, L.; Wang, W.; Chen, F.; Yang, T. Spectrochim.Acta A. 207,82: 7. [4] Fu, H.; Jiang, Du.; Zhou, R.; Yang, T.; Chen, F.; Li, H.;, Yin, Q.; Fan,Y. Food Anal. Method. 207, 55:324. [5] Fu, H.; Yin, Q.; Xu, L.; Goodarzi, M. Yang, T.; Li, G.; She,Y. Chemometr. Intell. Lab.206,57:43. [6] Fan,Y.; Liu, L.; Sun, D.; Lan, H.; Fu, H.; Yang, T.; She,Y.; Ni, C. Anal. Chim. Acta, 206, 96: 84. [7] Liu, L.; Fan,Y.; Fu, H.; Chen, F.; Ni, C.; Yin, Q.; Mu, Q.; Yang, T.; She,Y. Anal. Chim. Acta, 207, 963:9. 83

I-2-6 化学计量学与慢性肾病患者诊断 张卓勇 *, 张欣, 陈泽炜 首都师范大学化学系, 北京市海淀区西三环北路 05 号, 邮编 :00048 *Email: zhangzhuoyong@cnu.edu.cn 研究了基于模糊规则的专家系统 (FuRES) 和模糊最优联想记忆网络 (FOAM) 两种模糊分类器对于慢性肾病患者诊断的可行性 本工作还采用线性偏最小二乘判别分析 (PLS-DA) 作为对比 本文所用慢性肾病数据从 UCI 机器学习仓库下载 在测试数据中加入不同水平的噪声来评价模糊分类器的鲁棒性 首先, 将 个水平的正比噪声分别加入到训练集和预测集数据中, 得到 2 组模拟数据, 计算中对着 2 组数据的预测正确率进行比较 然后, 分别采用对上述数据进行分类判别 采用 20 次自助拉丁配分,FuRES 和 FOAM 的判别正确率分别为 98. ± 0.5% 和 97.2 ±.2% 在相同条件下,PLS-DA 的判别正确率为 94.3 ± 0.8% 将原始数据和模拟数据融合后再次使用上述方法建模和评价,200 次自助拉丁配分得到 FuRES 和 FOAM 的判别结果分别 99.2 ± 0.3% 和 99.0 ± 0.3% PLS-DA 的判别正确率为 95.9 ± 0.6% 结果表明,FuRES 和 FOAM 对慢性肾病患者的诊断均取得很好的效果,FuRES 的鲁棒性略好于 FOAM 这两种模糊分类器亦可用于其它疾病的诊断 [,2] 关键词 : 慢性肾病 ; 模糊规则专家系统 ; 模糊最优联想记忆网络 ; 偏最小二乘判别分析参考文献 [] Chen, Z.; Zhang, Z.; Zhu, R.; Xiang, Y.; Harrington, P. Chemometr. Intell. Lab., 206, 53:40. [2] Chen, Z.; Zhang, X.; Zhang, Z. Int. Urol. Nephrol., 206, 48:2069. * 通讯联系人 本工作得到北京市科技创新平台项目 (75303900) 资助 84

I-2-7 Appplication of Chemometrics in Untargeted Metabolomics Hongmei Lu, *, Zhimin Zhang, Hongchao Ji College of Chemistry and Chemical Engineering, Central South University, Changsha, 40083 *Email: hongmeilu@csu.edu.cn Untargeted metabolomics are rapidly becoming an important tool for studying complex biological samples. Modern analytical technologies afford comprehensive and quantitative investigation of a multitude of different metabolites. Typical metabolomics experiments can therefore produce large amounts of data. Handling such complex datasets is an important step that has big impact on extent and quality at which the metabolite identification and quantification can be made, and thus on the ultimate biological interpretation of results. This paper presents the key steps of metabolomics data acquisition and processing, and focuses on reviewing our group s work related to this topic, particularly on methods for handling data from chromatography-mass spectrometry experiments. Keywords: chemometrics; untargeted metabolomics; chromatography-mass spectrometry 85

I-2-8 复杂体系数学分离及精准定量研究进展 吴海龙 * 俞汝勤 ( 湖南大学化学化工学院 化学生物传感与计量学国家重点实验室, 长沙 40082; *Email: hlwu@hnu.edu.cn) 针对未知干扰共存复杂体系直接快速同时多组分定量分析难题, 发扬本室分析化学领域化学计量学基础研究处于国际前沿的特色及优势, 深入系统开展相关数学分离及高效定量方法创新性基础研究 通过优先发展三维及更多维分析仪器响应数阵数学分离分析新方法, 代替或简化相应化学和物理分离等步骤, 进而重点系统创新二阶 三阶及更高阶张量校正等化学多维校正新方法及新策略 结合三维荧光光谱 LC-DAD LC-MS 等高维分析手段, 优选研制三维及四维数学分离分析关键组件和在线量测装置, 显著提升静态及动态体系高效量测能力 深入开展生命 医学 药学 食品 环境 海洋等科学领域复杂体系感兴趣组分如蛋白质及特征肽段 氨基酸 抗癌药物 农药残留物 环境污染物等高效定量分析新方法基础应用研究 ; 系统发展动态生化体系如药物与 DNA 等相互作用 农残降解 药物代谢等过程近实时定量解析新手段 ; 为研制新型分析仪器及灵巧过程监控装置提供设计理论及技术依据 关键词 : 未知干扰共存复杂体系 ; 数学分离 ; 高效定量方法 ; 化学多维校正 ; 化学计量学 参考文献 : [] Y.N. Li, H.L. Wu*, et al. Analytica Chimica Acta, 200, 678: 26-33 [2] 卿湘东, 吴海龙 * 等. 中国科学 B: 化学,200, 40(): 655-663 [3] 聂重重, 吴海龙 * 等. 环境化学, 20, 30: 837-843 [4] Y.N. Li, H.L. Wu*,et al. Talanta, 20, 85: 325-332 [5] X.D. Qing, H.L. Wu*, et al. Talanta, 202, 03: 86-94 [6] X.D. Qing, H.L. Wu*, et al. Analytical Methods, 202, 4: 685-692 [7] X.D. Qing, H.L. Wu*, et al. Chemometrics and Intelligent Laboratory Systems, 204, 32: 8-7 [8] L.X. Xie, H.L. Wu*, et al. Chemom. Intell. Lab. Syst., 205,48, 9-9 [9] G.H. Wen, H.L. Wu*, et al. Chemom. Intell. Lab. Syst., 206, 55:62-72 [0] H.L. Wu*, Y. Li, C. Kang, R.Q. Yu*. In: Alejandro C. Olivieri, Graciela M. Escandar, Héctor C. Goicoechea, Arsenio Muñoz de la Peña, Eds., Fundamentals and Analytical Applications of Multi-way Calibration. Elsevier, 205, pp83-66 67-246 (ISBN 978-0-444-63527-3) 86

I-2-9 光谱形变定量分析理论及其应用研究进展 * 陈增萍 化学生物传感与计量学国家重点实验室, 湖南大学, 化学化工学院, 湖南, 长沙,40082 *Email: zpchen@hnu.edu.cn 目前, 在光谱定量分析的实践中采用的光谱定量分析理论基本上都是建立在兰伯比尔定律或类似的线性模型基础上的, 其前提是样本光谱的信号强度与样本中待测化学组分的浓度成线性关系 对于透明均相稀溶液体系来说, 这一假设基本上是成立的, 因此采用所测得的样本光谱信号的强度进行定量分析通常能够获得较好的结果 然而, 当待测样本为含有固相颗粒的非均相体系时, 所测得的样本光谱信号强度的变化不但包含待测物质含量变化的贡献, 而且还受样本物理性质以及仪器光学性质等因素的影响 所测得的样本光谱的信号强度与样本中待测化学组分浓度之间的关系就不再是简单的线性关系 建立在线性模型基础上的传统光谱定量分析理论就不再适用了 大约十年前, 本人提出一适用于复杂非均相体系光谱定量分析的新型光谱定量分析理论, 即光谱形变定量分析理论 -6 从那以后, 本研究小组对该理论的性能特点及其潜在应用领域进行了仔细研究和拓展 经过十多年的努力, 该理论的很多重要的性能和应用潜力得到了较充分的认识和发掘 该理论已被本研究小组用于解决很多在复杂体系光谱定量分析中所遇到的难题 然而, 由于该光谱定量分析理论与传统光谱定量分析理论之间存在着巨大的差异, 从事光谱定量分析工作的研究人员比较难以理解并应用该理论 为了推广该光谱定量分析理论, 本文详细介绍了该理论的理论基础及其性能特点, 并讨论了其在复杂体系光谱定量分析中的实际应用 关键词 : 非均相体系, 光谱形变定量分析理论, 乘效应模型 参考文献 [] Chen, Z.; Morris J., Martin, E. Anal. Chem. 2006, 78: 7674. [2] Chen, Z.; Zhong, L.; Nordon, A.; Littlejohn, D.; Holden, M.; Fazenda, M.; Harvey, L.; McNeil, B.; O Kennedy, R. Anal. Chem. 20, 83: 2655. [3] Jin, J.; Chen, Z.; Li, L.; Steponavicius, R., Thennadil, S., Yang, J.; Yu, R. Anal. Chem. 202, 84: 320. [4] Chen, Z.; Li, L.; Jin, J.; Nordon, A.; Littlejohn, D.; Yang, J.; Zhang, J.; Yu, R. Anal. Chem. 202, 84: 4088. [5] Chen, Y.; Chen, Z.; Yang, J.; Jin, J.; Zhang, J.; Yu, R. Anal. Chem. 203, 85: 205. [6] Chen, Y.; Chen, Z.; Long, S.; Yu, R. Anal. Chem. 204, 86: 2236. 87

I-3-0 Periodic and aperiodic order in soft matter systems An-Chang Shi,* Department of Physics and Astronomy, McMaster University, 280 Main Street West, Hamilton, Ontario Canada L8S 4M *Email: shi@mcmaster.ca The observation of ordered phases in condensed matter systems such as metallic alloys has a long history in materials physics. In recent years, intricate periodic and aperiodic order has emerged in a host of soft matter systems including supramolecular assemblies, surfactants and block copolymers. The occurrence of complex phases in these diverse systems underscores the universality of emergent order in condensed matter. For the case of block copolymers, recent experimental and theoretical studies have revealed that non-classical ordered phases, such as quasicrystals and the Frank-Kasper and Laves phases, could emerge from block copolymers as equilibrium or metastable morphologies. As such, block copolymers provide an ideal system to study the origins and stability of periodic and aperiodic order in condensed matter physics. In my presentation, I will summarize recent theoretical and experimental progresses on this fascinating topic and discuss possible future research directions. Keywords: self-assembly; ordered phases; block copolymers 88

I-3-02 过冷液体结构与动力学的计算机模拟 孙昭艳 * 中国科学院长春应用化学研究所, 长春市人民大街 5625 号,30022 *Email: zysun@ciac.ac.cn 玻璃广泛存在于自然界中 然而, 人们对玻璃化转变这一现象的物理本质仍然没有足够清晰的认识 Anderson 在 995 年时曾指出 : 在固态理论中, 最深远 最有兴趣 尚未解决的问题可能是玻璃和玻璃化转变本质的理论, 这可能是将来 0 年中的又一个突破 事实上, 这一难题在二十年之后仍未得到有效的解决 在玻璃化转变点附近关联长度趋于无穷, 因而目前科学家大多从过冷液体的角度或从固体物理的角度阐释玻璃化转变的本质 对于过冷液体来说, 其二体关联结构与一般液体十分类似, 而在趋向于玻璃化转变点的过程中却出现了动力学性质的急剧变慢, 表现出结构和动力学之间的去耦合 本工作基于计算机模拟方法, 探究了几种典型过冷液体的结构与动力学性质, 试图从结构和动力学的角度理解玻璃化转变的物理本质 关键词 : 玻璃化转变 ; 结构 ; 动力学参考文献 [] Li, Y., Zhu, Y., Sun, Z., Phys. Rev. E, 206, 94, 06260 [2] Li, Y., Zhu, Y., Sun, Z., J. Chem. Phys., 205, 42, 24507 89

I-3-03 刚 - 柔嵌段高分子的自组装结构及相变路径 唐萍, 孙同杰, 刘法强, 邱枫 聚合物分子工程国家重点实验室, 复旦大学高分子科学系, 上海,200433 刚 - 柔 (Rod-coil) 嵌段高分子由柔性与刚性嵌段通过化学键相连, 近年来在功能材料领域的应用前景得 到了人们越来越广泛的关注 尤其是以共轭高分子作为刚性嵌段的一类聚合物, 由于共轭结构的半导体和 光学特性, 使其在有机光电器件领域的开发得到了深入研究 [] 这类材料的应用需要形成大面积的 0nm 尺 度的纳米微区, 以便高效地实现电荷传输和收集 [2] 而刚 - 柔嵌段高分子的刚性和柔性嵌段可以分别作为电 子供体和受体, 自组装成具有 0nm 相区尺寸的微观结构, 其光电效率比纯的刚性均聚物以及刚性 / 柔性链 高分子共混物更佳 由于材料的性能取决于其微相分离结构, 因此需要理解和预测刚 - 柔嵌段高分子的相形 态以及形成机理 然而, 刚 - 柔嵌段高分子的自组装行为与传统柔性两嵌段高分子显著不同, 一是体系中不仅由于化学组 成的差异性产生各向同性相互作用, 而且由于链节的刚性效应产生各向异性取向相互作用 ; 另一方面, 刚 性和柔性链在分子链尺寸的描述上也有显著不同 因此, 刚 - 柔嵌段高分子体系的相图具有明显的不对称性, 而且层状相稳定区域明显变大 总之, 刚 - 柔嵌段高分子体系具有更为复杂的参数空间, 既存在微相分离与 取向相互作用的耦合, 又存在刚性与柔性链之间的尺寸差异效应 这些因素必然导致刚 - 柔嵌段高分子体系 中具有特殊的分子链排列规律, 从而表现出特殊的液晶相行为和微观聚集形态 本文采用自洽场理论 (SCFT) 并结合弦方法, 模拟了刚 - 柔嵌段高分子中的非层状液晶结构的形成及影响因素, 并对这些有序 - 有序相结 构之间的转变路径进行分析, 明确其相变机制及路径中的亚稳态结构, 为实验上制备特定的复杂液晶结构 提供理论依据 关键词 : 刚 - 柔嵌段高分子 ; 自洽平均场理论 ; 弦方法 参考文献 [] Olsen B D and Segalman R A. Self-assembly of rod-coil block copolymers[j]. Materials Science & Engineering R-Reports, 2008, 62(2): 37-66. [2] Segalman R A, et al. Block copolymers for organic optoelectronics[j]. Macromolecules, 2009, 42(23): 9205-926. 90

I-3-04 Molecular dynamics simulation of the response of bi-disperse polyelectrolyte brushes to external electric fields Chaohui Tong,*, Fen Zhang, Huanda Ding, Chao Duan, Shuangliang Zhao 2 Department of Physics, Ningbo University, 88 Fenghua Road, Ningbo, 352 2 Department of Chemical Engineering, East China University of Science and Technology, 30 Meilong Road, Shanghai, 200237 *Email: tongchaohui@nbu.edu.cn Langevin Dynamics simulations have been performed to investigate the response of bi-disperse and strong polyacid chains grafted on an electrode to electric fields generated by opposite surface charges on the polyelectrolyte(pe)-grafted electrode and a second parallel electrode. Simulation results clearly show that, under a negative external electric field, the longer grafted PE chains are more strongly stretched than the shorter ones in terms of the relative change in their respective brush heights. Whereas under a positive external electric field, the grafted shorter chains collapse more significantly than the longer ones. It was found that, under a positive external electric field, the magnitude of the total electric force acting on one shorter PE chain is larger than that on one longer PE chain, or vice versa. The effects of smeared and discrete charge distributions of grafted PE chains on the response of PE brushes to external electric fields were also examined. Keywords: polyelectrolyte brushes; polydispersity; Langevin Dynamics; electric fields References: [] Tong, C. Chem. Phys. 205, 43: 054903. [2] Kang, C.; Zhao, S.; Tong, C. Chinese J. Polym. Sci. 207, 35: 98. 9

I-3-05 聚电解质溶液相分离理论 苗兵 中国科学院大学, 北京,0408 Email: bmiao@ucas.ac.cn 聚电解质体系是高分子物理乃至统计物理中具有基础重要性的研究对象, 电荷间长程库仑作用使得聚电解质溶液表现出众多不同于中性高分子溶液的新颖行为 本文在统计力学的框架里写出描述聚电解质溶液浓度涨落的有效自由能模型, 该模型表现出 Lifshitz 行为, 考察离子强度和链统计性对溶液相分离的影响 本文进一步对超越 RPA 方法的理论方法进行探讨 关键词 : 聚电解质 ; 相分离 ; 统计场论 92

I-3-06 共聚物引导自组装的动力学调控 张良顺,*, 林嘉平 华东理工大学, 材料科学与工程学院, 上海市梅陇路 30 号 200237 *Email: zhangls@ecust.edu.cn 快速地获得宏观有序纳米结构是共聚物应用于半导体工业中急需解决的问题之一 溶剂蒸气退火和区域退火是两种典型的调控共聚物长程有序结构的动力学方法 本工作建立这两种退火方法的动力学模型, 并理解和探索共聚物引导自组装的有序行为及缺陷湮灭机制 基于动态自洽场理论, 发展一种相互参数依赖于时空变化的局域退火模型, 讨论前端移动速率 墙壁选择性和相互作用参数等因素对嵌段共聚物自组装纳米结构有序机理和取向调节的影响规律 当嵌段共聚物自组装机理由自发有序转变为模板有序或缺陷湮灭时, 纳米结构有序程度显著提升 另外, 处理溶剂蒸气退火模型的移动边界问题, 模拟共聚物溶液的溶剂摄入 - 蒸发过程, 得到有序程度提升的共聚物纳米结构, 与其它模拟方法和实验结果基本吻合 Fig. (a) Zone annealing model for the block copolymers. (b) Morphological evolution of block copolymers in the process of solvent evaporation 关键词 : 引导自组装 ; 区域退火 ; 溶剂蒸气退火 ; 动态自洽场理论参考文献 [] Zhang, L.; Wang, L.; Lin, J. ACS Macro Lett. 204, 3: 72. [2] Cong, Z.; Zhang, L.; Wang, L.; Lin, J. J. Chem. Phys. 206, 44: 490. [3] Wan, X.; Tao, G.; Zhang, L.; Lin, L. Phys. Chem. Chem. Phys. 207, 9: 6707. 93

I-3-07 Experimental and Theoretical Study on Supported Nanocatalysts Jianguo Wang College of Chemical Engineering, Zhejiang University of Technology, Hangzhou, 30032 P. R. China *Email: jgw@zjut.edu.cn Supported noble metal catalysts have played an important role in the conversion of energy and resources. Computational simulations ranging from quantum chemistry density functional calculations, molecular dynamic have been widely used to investigate the reaction mechanisms and the relationship between structure and properties of nanocatalysts. However, there are still huge gaps between computational simulations and realistic experiments. During the recent years, we try to computational simulate the nanocatalysts by consideration of realistic conditions in order to reduce the pressure and materials gap. References. J.Zheng, X. Chen, X.Zhong, S.Li, T.Liu, G.l. Zhuang, X.N. Li, S.Deng, D.Mei, J.-G.Wang*., Adv. Funct. Mater.,207,accepted. 2. X. Zhong, Y. -Y. Sun, X. -L. Chen, G. -L. Zhuang, X. -N. Li, and J.-G.Wang*., Adv. Funct. Mater., 206, 26, 5778 3. X. -Y. Tao #, J. -G. Wang #,et al., Nat. Commun., 206, 7, 203. 4. Y. -J. Gao #, P. Tang #, H. Zhou, W. Zhang, H. -J. Yang, N. Yan, G. Hu, D. -H. Mei, J. -G. Wang*, D. Ma*., Angew. Chem. Int. Ed., 206, 55, 324-328. 5. Q. -X. Cai, J. -G. Wang*, et al, AIChE J., 205, 6, 382-3824. 6. D. -F. Gao #, H. Zhou #, J. Wang, S. Miao, F. Yang, G. -X. Wang*, J. -G. Wang*, X. -H. Bao., J. Am. Chem. Soc., 205, 37, 4288-429. 94

I-3-08 SCFT Study on the Self-Assembly of Block Copolymers Weihua Li,*, Chao Duan, Mingtian Zhao, Yicheng Qiang State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, Shanghai, 200433 *Email: weihuali@fudan.edu.cn Since 960s when Edwards introduced the Path Intergral method to describe the configurations of polymer, Self-consistent field theory (SCFT) has been gradually developed into a standard and powerful tool for the study of block copolymer self-assembly. Accordingly, SCFT has played an irreplaceable role on advancing the understanding of block copolymer self-assembly, which is complementary to some frequently-used experimental measurements like small-angle X-ray scattering (SAXS), atomic force microscope (AFM) and tranmission electron microscope (TEM). SCFT has a few prominent advantages. First of all, it is able to accurately calculate the free energy of each ordered phase and thus to construct the phase diagram. Second, SCFT is easy to deal with any topological architectures and thus is widely used. Third, SCFT can provide the distribution of each segment that is beneficial to the understanding of the self-assembly mechanism of an ordered phase. In addition, the entropic and enthalpic contributions can be readily extracted from SCFT, which plays another important role to unveiling the self-assembly mechanism. In this presentation, we will talk about our recent work about the SCFT studies on the self-assembly of a few purposely designed block copolymer systems leading to the formation of unconventional periodic (mesocrystal) and aperiodic (quasicrystal) nanostructures [-5]. Keywords: self-consistent field theory (SCFT); block copolymer; self-assembly; mesocrystal; quasicrystal References: [] Xie, N.; Liu, M. J.; Deng, H. L.; Li, W. H*.; Qiu, F.; Shi, A. C. J. Am. Chem. Soc. 204, 36: 2974-2977. [2] Liu, M. J.; Xia, B. K.; Li, W. H.*; Qiu, F.; Shi, A. C. Macromolecules 205, 48:3386-3394. [3] Gao, Y.; Deng, H. L.; Li, W. H.*; Qiu, F.; Shi, A. C. Phys. Rev. Lett. 206, 6: 068304. [4] Liu, M. J.; Qiang, Y. C.; Li, W. H.*; Qiu, F.; Shi, A. C*. ACS Macro Lett. 206, 5: 67-7. [5] Duan, C.; Li, W. H.*; Qiu, F.; Shi, A. C. ACS Macro Lett. 207, 6: 257-26. 95

I-3-09 脂筏促进细胞粘附蛋白的键合 胡晶磊,*, 李龙 2,, 宋凡 2,*, 南京大学匡亚明学院, 南京市栖霞区仙林大道 63 号 20023 2 中国科学院力学研究所, 北京市北四环西路 5 号 0090 *Email: hujinglei@nju.edu.cn 细胞膜铆定蛋白之间的键合调控着细胞粘附和信号传导, 对键合作用的深刻认识有助于理解细胞间通讯所驱使的多种生理过程 脂筏作为细胞膜上富含胆甾醇和饱和磷脂的微相区, 被认为是募集蛋白质分子以实现生物功能的重要平台 一个重要而未决的问题是脂筏如何影响细胞膜铆定给体和受体蛋白的键合平衡常数 我们采用经典的生物膜介观模型, 使用 Monte Carlo 方法研究多组分膜的粘附, 发现细胞膜铆定给体和受体蛋白在脂筏上的优先分配通过与热激发引起的细胞膜形状涨落协作而显著提高键合常数 有趣的是, 键合常数甚至可以大于基底支撑膜上相同蛋白的键合常数 与单组分细胞膜的情况 [] 相反, 细胞膜的形状涨落有助于铆定给体和受体蛋白的键合 我们的研究结果表明, 真实细胞可以通过调控脂筏的性质, 比如其在细胞膜上的面积分数 尺寸以及与蛋白的亲和性, 来控制粘附蛋白的键合 [2] 关键词 : 细胞粘附 ; 脂筏 ; 膜蛋白 ; 特异性键合参考文献 [] Hu, J.; Lipowsky, R.; Weikl, T.R. PNAS. 203, 0: 5283. [2] Li, L.; Hu, J.; Shi, X.; Shao, Y.; Song, F. Soft Matter. 207, 3: 4294. 96

I-3-0 稳态剪切下高分子的构象 动力学及流变性质 陈继忠 * 中国科学院长春应用化学研究所, 高分子物理与化学国家重点实验室, 长春市人民大街 5625 号, 邮编 : 30022 *Email: jzchen@ciac.ac.cn 采用多粒子碰撞动力学 (MPCD) 和非平衡态分子动力学模拟 (NEMD) 方法, 我们研究了不同链拓扑结构的高分子在稳态剪切场下的构象 动力学和流变性质, 揭示流场诱导构象转变与拓扑结构之间的关系, 并从链拉伸 取向 流场诱导动力学及缠结效应等角度深入阐述了高分子流体的剪切变稀行为的微观机理, 初步明晰了结构与粘度之间的对应关系 这些研究进一步从微观角度认识了高分子流体非线性流变行为 关键词 : 多粒子碰撞动力学 ; 非平衡态分子动力学 ; 高分子 ; 剪切变稀 97

I-3- 固载离子液体吸收 CO 2 吕玲红 *, 汤子仟, 谢文龙, 陆小华 南京工业大学化工学院, 材料化学工程国家重点实验室, 南京,20009 *Email: :linghonglu@njtech.edu.cn 当前,CO2 减排问题已成为全球关注的焦点, 高效分离 CO2 迫在眉睫 CO2 处理量巨大, 现有装置规模 庞大 成本高昂 例如, 目前发展相对成熟的乙醇胺溶液法, 吸收解吸设备规规模过大, 捕集 CO2 费用高, 不符合低能耗 低成本捕集 CO2 的目标, 亟需大幅强化过程 离子液体法吸收分离被美国能源部列为未来重 点发展的碳捕集技术之一, 但离子液体价格高昂 气液传质速率又极低, 阻碍其大规模应用 亟需对过程 进行强化 将离子液体担载成膜是目前的研究热点, 其本质是通过增强表界面来提高速率, 强化过程 然 而, 担载之后离子液体膜中纳微界面的复杂结构及其复杂作用使得机制的研究变得困难, 从而造成材料设 计制备和应用缺乏强有力的理论指导 基于此, 我们设计实验制备不同膜厚的负载离子液体, 以及通过改变载体和离子液体种类构建不同界 面, 旨在定量考察膜厚和界面对于离子液体吸收分离 CO2 性能的影响 将 [Hmim][NTf2] 这种离子液体担载在 P25 上后发现, 担载后其 CO2 饱和吸收量大幅提高, 且吸收量与体相的差别随着膜厚减小而越来越大 饱和 吸收量提高将使得过程推动力增强, 有利于过程速率通量的大幅强化 研究发现担载后吸收量提高的现象 受到离子液体本身以及载体的影响, 也就是界面的影响 如何定量分析上述实验现象, 解释其背后机理, 以及调控机制至关重要 包括分子模拟和实验研究在 内的越来越多的文献报道, 离子液体受限后往往表现与体相完全不同的特殊现象, 然而目前为止, 受限效 应的可能机理尚不清楚 因此我们利用分子动力学 (MD) 模拟 CO2 在负载于 TiO2/ 石墨表面的 [hmim][tf2n] 离子液体的吸收 结果发现大多数离子液体分子吸附在固液界面处, 而 CO2 大部分吸收在气液界面处 CO2 扩散系数随离子液体的厚度减少而增加, 这与实验结果在趋势上是一致的 我们还考察了体系的倾斜角分 布, 发现阴离子和 CO2 在固体界面的角度分布比较分散, 而阳离子在各处的角度分布都是 90 度角比较多 但 随着厚度的增加, 阴离子和 CO2 在固体界面角度分布特征渐渐变得不明显 说明固体界面的受限作用影响了 阴离子和 CO2 分子的相互作用 由于表面性质的重要性, 我们研究了不同表面性质的影响, 与氧化钛表面体 系相比, 发现只有少量 CO2 分子吸附在石墨 / 离子液体界面, 石墨表面能提高 CO2 在离子液体中的扩散系数 说明疏水性表面不但也能起到强化吸收的作用, 还能提高其扩散性质 本研究结果对于固载离子液体吸收 CO2 的微观机理和实验设计有一定的指导意义 关键词 : 二氧化碳 ; 吸收 ; 离子液体 ; 界面 98

I-3-2 高效 O 2 CO 2 活化催化剂设计 合成及应用 胡兴邦 *, 吴有庭,*, 张志炳 南京大学化学化工学院, 江苏南京,20023 *Email: huxb@nju.edu.cn, ytwu@nju.edu.cn [] 碳氢化合物的活化及氧化是将石油化工及煤化工初级原料转化为有用化工产品的重要途径, 采用氧气 (O2) 来活化并氧化碳氢化合物是一种廉价 环境友好的方法 以二氧化碳 (CO2) 为原料来合成有用的化工 [2] 产品是实现 有机会 二氧化碳 有机物 碳循环的理想途径 但 O2 和 CO2 均比较惰性, 在没有催化剂参与的情况下很难和其他底物进行反应, 开发高效催化剂来活化 O2 和 CO2 是实现氧气氧化剂及二氧化碳综合利用的核心科学问题 细胞色素 P450 活性中心卟啉金属化合物是目前发现的效率最高的 O2 活化催化剂之一, [] 但其合成过程复杂 综合收率低, 使得此类催化剂价格一直非常昂贵 通过采用计算机大量筛选催化剂, 考察催化剂结构变化对活性影响规律的基础上 (Fig. ), 我们开发了系列高活性氧气活化催化剂, 如 : 离子液体支载乙酰丙酮催化剂 离子液体支载醋酸盐催化剂 新型卡宾金属催化剂 新型希夫碱催化剂等, 其中部分催化剂甚至表现出了比金属卟啉更高的室温催化活性, 以上催化剂在以 O2 为氧化剂的烯烃环氧化 烷烃氧化等过程中获得了较好的催化效果 此外, 采用计算机辅助设计的方法, 我们还开发了系列高活性 CO2 活化催化剂, 如新型卡宾铜催化剂 离子液体催化剂等, 以上催化剂在以 CO2 为原料合成碳酸二甲酯 酰胺 甲酸等反应中获得了较好的催化效果 [3-8] 关键词 : 氧气 ; 二氧化碳 ; 活化 ; 结构 - 活性关系 参考文献 Fig. 离子液体支载催化剂结构 - 活性关系 [] 胡跃飞, 林国强, 现代有机反应 : 氧化反应,2008 年第一版, 化学工业出版社 [2] Pera-Titus M., Chem. Rev., 204, 4:43-492. [3] Hu, X. B.; Sun, Y.; Mao, J. Y.; Li, H. R. J. Catal. 200, 272: 320-332. [4] Hu, X. B.; Liu, C. Y.; Wu, Y. T.; Zhang, Z. B. J. Phys. Chem. C 20, 5, 2393-2392. [5] Hu, X. B.; Martin, D.; Melaimi, M.; Bertrand, G. J. Am. Chem. Soc. 204, 36: 3594-3597. [6] Hu, X. B.; Soleihavoup, M.; Melaimi, M.; Chu, J. X.; Bertrand, G. Angew. Chem. Int. Ed. 205, 5: 6008-60. [7] Zhao, T. X.; Hu, X. B.; Wu, D. S.; Li, R.; Yang, G. Q.; Wu, Y. T. ChemSusChem, 207, 0: 2046-2052. [8] Xu, Y.; Hu, X. B.; Shao, J.; Yang, G. Q.; Wu, Y. T.; Zhang, Z. B. Green Chem. 205, 7: 532-537. 99

I-3-3 通过调节蒸发速率实现分层胶体薄膜的制备 周嘉嘉,2,*, 蒋滢,2, 土井正男 2 北京航空航天大学化学学院 仿生智能界面科学与技术教育部重点实验室 2 软物质物理及其应用研究中心 北京市海淀区学院路 37 号,009 * jjzhou@buaa.edu.cn 摘要 : 包含不同大小胶体粒子的溶液薄膜在蒸发过程中会出现大小球的分层, 小球在上而大球在下 [] 这 与传统理论的预测正好相反 因为大球的扩散常数比小球小, 所以更容易在气液界面上堆积 我们运用昂 萨格原理, 在经典扩散模型中引入大小球之间的相互作用, 成功的解释了这一反常的分层现象 [2] 我们的 理论结果对于运用蒸发一次性制备分层的薄膜具有指导性意义 关键词 : 溶剂蒸发, 大小球分层, 胶体溶液, 昂萨格原理 参考文献 [] Fortini, A.; Martín-Fabiani, I.; de la Haye, J. L.; Dugas, P.-Y.; Lansalot, M.; D'Agosto, F.; Bourgeat-Lami, E.; Keddie, J.L.; Sear, R.P.; Dynamic Stratification in Drying Films of Colloidal Mixtures, Phys. Rev. Lett., 206, 6:830 [2] Zhou, J.J.; Jiang, Y.; Doi, M.; Cross Interaction Drives Stratification in Drying Film of Binary Colloidal Mixtures, Phys. Rev. Lett. 207, 8:08002 00

I-3-4 高分子结晶的局域跃迁模型 肖弘毅, 张兴华 2, 严大东,* 北京师范大学物理系, 北京,00875 2 北京交通大学理学院, 北京,00044 *Email: yandd@bnu.edu.cn 高分子晶区 - 无定形区界面的结构控制着高分子片晶的性能 在界面层的长度尺度上, 界面能很大程度上依赖于高分子链的持久长度和接入点间距 高分子链段通过茎干在与自身垂直方向上的局域跳迁释放其界面张力 对于给定的界面层厚度, 界面结构依赖于接入点间距分布 在本工作中, 我们建立了一个基于蠕虫状链模型的局域跃迁模型, 采用单链平均场理论对分别由规则折叠与松散折叠组成的界面进行研究, 从而对高分子晶体界面的形成过程给出了一种可能的解释, 即晶区内茎干会发生侧向的局域跃迁运动 利用王 - 朗道算法, 我们求出了单链平均场理论中配分函数的精确数值解 对于不同的 loop 长度, 理想接入点间距由高分子链的弯曲能与构象熵的竞争决定, 其结果为近邻折叠模型提供了证据 此外, 为了同时满足全局能量空间内的信息完备性与局域低能空间内的信息精确性, 我们还发展了一种行之有效的多步式高精度修订版的王 - 朗道算法 关键词 : 高分子结晶 ; 蠕虫链模型 ; 单链平均场 ; 局域跃迁模型 0

I-3-5 Polymer Escape from Confining Nanotube in Reverse Flow Mingming Ding, Tongfei Shi * State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 30022 *Email: tfshi@ciac.ac.cn The rapid developments in fabrication of nanometer-scale fluidic devices have provided a variety of new strategies for exploring the molecular behavior on the single-molecule level, and resulted in a broad range of applications in biotechnology and medicine. When the scale of a nanofluidic device is comparable to the size of an enclosed polymer, the effect of the confinement from the nanofluidic device can cause the increase in the free energy of the polymer due to the reduction in its allowed conformations, which appears in a variety of situations including polymer translocation through a nanopore or polymer escape from the nanotube. Using a hybrid simulation method that combines a lattice-boltzmann approach for the flow and a molecular dynamics model for the polymer, we investigated the polymer escape from a confining nanotube in a reverse flow. We demonstrate the substantial disparity in escape dynamics of the confined polymer for the cases with and without the reverse flow. Our simulations confirm the existence of a reverse critical velocity flux, which results from a balance between the entropic force (confinement free energy) and the hydrodynamic force (velocity of the flow). Our work confers new insights into understanding the microscopic dynamics of the polymer escape from a confining nanotube in a reverse flow, and provide guidance for the design of functionalized nanometer-scale fluidic devices. Fig. Escape probability P e(j) as a function of the velocity flux J at different diameters of the confining nanotube. Inset: reverse critical velocity flux J c,e as a function of the diameter of the confining nanotube D. Keywords: polymer escape; confining nanotube; reverse flow References: [4] Klushin, L. I.; Skvortsov, A. M.; Hsu, H. P.; Binder, K. Macromolecules 2008, 4: 5890 5898. [5] Ding, M.; Chen, Q.; Duan, X.; Shi, T. J. Chem. Phys. 206, 44: 74903. 02

I-3-6 The Drying of Liquid Droplets Xingkun Man,* Center of Soft Matter Physics and its Applications, Beihang University, Beijing 009, China 2 School of Physics and Nuclear Energy Engineering, Beihang University, Beijing 009, China *Email: manxk@buaa.edu.cn The drying of liquid droplets is a common daily life phenomenon that has long held a special interest in scientific research. We propose an Onsager variational principle theory that describes the droplet shape evolution and predicts the deposit distribution of nonvolatile components on the substrate. It is shown that for the drying of a single droplet, the deposition pattern changes continuously from a coffee ring to volcanolike and to mountainlike depending on the mobility of the contact line and the evaporation rate. When drying of two neighboring droplets, asymmetrical ring-like deposition patterns are formed, including fanlike and eclipse-like deposition patterns. The same theoretical model also explained the observed attraction-repulsion-chasing behaviors of evaporating droplets, where the droplets are not pinned. Evaporating droplets are known to show complex motion that has conventionally been explained by the Marangoni effect (flow induced by the gradient of surface tension). We show that the droplet motion can be induced even in the absence of the Marangoni effect due to the gradient of evaporation rate. Fig. Evaporation effect actuates droplet moving from high evaporation side to low evaporation side Keywords: liquid droplets; evaporation; deposition pattern; droplet motion References: [] X. K. Man*, and M. Doi*, Phys. Rev. Lett. 207, accepted. [2] S. Y. Hu, Y. H, Wang, X. K. Man*, and M. Doi, Langmuir 207, 33: 5965. [3] X. K. Man, and M. Doi*, Phys. Rev. Lett. 206, 6: 0660. 03

I-3-7 溶液中粒子聚集自组装热力学模拟研究 何学浩 * 天津大学理学院化学系, 天津市津南区海河教育园区雅观路 35 号,300350 *Email: xhhe@tju.edu.cn 自然界中粒子聚集自组装现象广泛存在, 如 : 溶液中各种晶体的形成和病毒蛋白壳结构的形成等, 粒子聚集热力学机理的深入认识在纳米材料领域具有重要基础理论意义 我们采用副本交换布朗动力学模拟方法系统研究了球形和多面体粒子在溶液中的聚集热力学行为, 模型采用隐式溶剂方法, 粒子间作用势采用列表作用势方法, 通过模拟分析计算出粒子聚集自由能曲线, 从而阐明了粒子聚集行为同粒子形状和温度的依赖关系, 并同经典成核理论进行了比较, 指出了经典理论的问题及根源, 该模拟结果为如何调控粒子成核自组装提供了理论指导 Fig. The self-assembly structures of polyhedral particles 关键词 : 自组装 ; 多面体粒子 ; 布朗动力学模拟参考文献 [] Xu, J.; Wang, Y. L.; He, X. H. Soft Matter 205,, 7433. [2] Wang, Y. L.; He, X. H. RSC Adv., 206, 6, 6608. Simulation of Thermodynamics of Self-assembly of Particles in Solution Xuehao He * [] Department of Chemistry, School of Science, University of Tianjin, Tianjin, 300350 Abstract: The particle aggregations in solution widely exist in nature, such as all kinds of crystal formation and viral protein shell formation. Understanding thermodynamics of particle assembly has fundamental importance in the field of nanomaterials. We applied replica-exchange Brownian dynamics to study the thermodynamics of self-assembly of spherical and polyhedral particles in solution. Our model used an implicit solvent method, and the particle interaction used the tabulated potential technology. Through simulation, the free energy curve of particle aggregation is achieved and further compared with the classical nucleation theory. The dependences of particle assembly behaviors on particle shape and temperature are clearly shown. This work provides a guidance about how to regulate the nucleation and growth of particle self-assembly in experiments. 04

I-3-8 纳米粒子在细胞膜上的扩散动力学 : 分子模拟及理论分析 * 燕立唐 清华大学化学工程系高分子研究所, 北京,00084 *Email: ltyan@mail.tsinghua.edu.cn 研究具有复杂拓扑结构和具有特殊功能化的纳米粒子在细胞膜上的扩散动力学对于明晰纳米粒子与生物膜的相互作用, 了解其细胞毒性, 进而开发纳米粒子在生物医学领域的潜在应用来说具有重要的理论和实际意义 然而, 囿于极小的空间尺度和极短的时间尺度, 很难单纯通过实验研究来解决此问题, 计算机模拟因而成为洞悉该过程的有效途径 针对此问题, 本课题组采用介尺度模拟的方法, 开展了对带电球形纳米粒子和两维石墨烯纳米片在细胞膜上扩散动力学的计算机模拟和理论分析 本论文即介绍我们在带电球形纳米粒子和两维石墨烯纳米片的细胞膜上扩散动力学的模拟研究工作 一方面, 关于球形纳米粒子, 我们揭示了其扩散行为对于纳米粒子的电性和表面电荷的空间分布的依赖性 相较于电中性粒子在细胞膜上的菲克扩散, 表面电荷随机分布的带电球形粒子在细胞膜上进行定向输运, 然而表面电荷均匀分布的粒子更倾向于增强的菲克扩散 同时通过建立理论模型和理论分析, 阐明了该差异是由静电导致的膜涨落和表面重构引起的 另一方面, 通过运用介尺度的计算机模拟, 我们揭示了由细胞膜表面破缺引起的石墨烯在生物膜内从布朗运动到 lévy 扩散, 最后形成定向运输的独特的扩散动力学 同时, 基于细胞膜表面的能量分析, 阐明了不同的石墨烯与细胞膜的相互作用所对应的细胞膜表面孔的稳定程度, 从而导致了石墨烯在细胞膜内不同的扩散行为 这些工作对于揭示石墨烯等两维纳米材料和带电性的纳米材料潜在的细胞毒性, 进而理解其对人体健康的危害性, 以及在纳米医学等领域的深入应用具有比较重要的促进作用 关键词 : 扩散动力学 ; 细胞膜 ;Levy 行走 ; 分子模拟参考文献 [] Chen, P.; Huang, Z.; Liang, J.; Cui, T.; Zhang, X.; Miao, B.*; Yan, L.-T.* ACS Nano 206, 0: 54. [2] Mao, J.; Chen, P.; Liang, J.; Guo, R.; Yan, L. T.* ACS Nano 206, 0: 493. [3] Liang, J.; Chen, P.; Dong, B.; Huang, Z.; Yan, L. T.* Biomacromolecules 206, 7:834. [4] Guo, R.; Mao, J.; Yan, L. T.* ACS Nano 203, 7: 0646. [5] Chen, P. Y..; Mao, J.; Yan, L. T.* Submitted. 05

I-3-9 多肽与细胞界面相互作用机制研究 杨恺 *, 元冰, 马余强 2 苏州大学, 江苏省苏州市十梓街 号,25006 2 南京大学, 江苏省南京市汉口路 22 号,20093 *Email: yangkai@suda.edu.cn 基于抗菌肽 (AMP) 的药物设计是解决细菌耐药性以及超级细菌的一条重要途径 然而, 人们对于抗菌肽与膜的相互作用机制尚缺乏清楚的认识 在本工作中, 我们以蜂毒肽作为抗菌肽模型, 结合计算机分子动力学模拟, 采用用不同生物膜模型和实验技术, 在分子层次上着重研究了蜂毒肽与生物膜的界面相互作用动力学过程 研究发现, 蜂毒肽在脂双层上的初始吸附和聚集行为会导致脂膜发生剧烈的波动和局部形变 ; 尤其是, 会聚的多肽分子引发了脂双层中外叶脂分子的抽离以及脂膜的质量损失 由此引发的生物膜脂双层不对称性将促使蜂毒肽插入膜中, 之后它对脂膜内叶脂分子的扰动会引起最终跨膜孔的形成 此外, 通过对蜂毒肽进行空间微结构设计, 我们进一步探讨了多肽分子之间的协作作用对其生物膜活性的影响 这些发现将深化我们对多肽抗菌机制的了解, 为开发高效低毒的新型抗菌药物提供应用性指导 关键词 : 抗菌短肽 ; 细胞界面 ; 膜结构 ; 相互作用机制 06

I-3-20 两性离子聚电解质毛刷表面自清洁机理的模拟研究 朱有亮, 吕中元 2, 孙昭艳,* 中国科学院长春应用化学研究所, 长春市人民大街 5625 号, 邮编 30022 2 吉林大学理论化学研究所, 长春市朝阳区柳条路 2 号, 邮编 30023 *Email: zysun@ciac.ac.cn 近些年来受血红细胞表面细胞膜自清洁现象的启发, 人们发展了可以产生自清洁作用的仿生的两性离 [-3] 子聚电解质毛刷材料, 比如带有磷酸胆碱基团的 poly(2-methacryloyloxylethyl phosphorylcholine) (PMPC) PMPC 毛刷表面具有完全的疏油特性, 不仅体现在水润湿状态下, 即使在干燥状态下吸附了油污后, 也可 [4,5] 以通过水的作用, 快速 自动地去除油污 不是所有的超亲水材料都能够产生自清洁作用, 因此对于自清洁作用产生的机理目前还不是很清楚 我们利用分子动力学方法结合极化 MARTINI 力场, 通过建立体系 [6] 的粗粒化模型, 对接枝 PMPC 的毛刷表面产生自清洁现象进行了模拟研究 我们在模拟中重现了 PMPC 表面产生自清洁现象的过程, 从微观角度解析了自清洁作用产生的机理 我们发现自清洁作用是由于 PMPC 分子的超亲水性以及毛刷内部的稳定结构, 使得水分子能够渗透到 PMPC 分子层中与两性离子发生水和作用, 促使油分子与其剥离 在自清洁过程中 PMPC 的接枝长度 密度和结构都会影响材料的自清洁效率 关键词 : 分子动力学 ; 自清洁材料 ;PMPC; 粗粒化 Fig. The coarse-grained model in molecular dynamics simulation 致谢 : 感谢国家自然科学基金 ( 基金号 240402, 2534004, 2474) 和吉林省科学和技术发展计划 ( 项目号 204059004JH) 资助. 参考文献 [6] R. F. A. Zwaal, A. J. Schroit, Blood, 997, 89, 2. [7] M.-C. Sin, S.-H. Chen, Y. Chang, Polym. J., 204, 46, 436. [8] S. Jiang, Z. Cao, Adv. Mater., 200, 22, 920. [9] J. B. Schlenoff, Langmuir, 204, 30, 9625. [0] K. He, H.-R Duan, G. Y. Chen, X.-K. Liu, W.-S. Yang, and D.-Y. Wang, Acs Nano, 205, 9, 988. [] Z. Wu, Q. Cui, and A. Yethiraj, J. Phys. Chem. B, 200, 4, 0524. 07

I-3-2 高分子表面吸附的模拟研究 罗孟波 浙江大学物理系 杭州 30027 Email: luomengbo@zju.edu.cn 高分子薄膜广泛应用于材料保护 表面润滑 光学涂层 印刷涂层等领域 高分子的表面性质主要由 表面附近高分子的性质决定 但高分子与表面的相互作用强烈影响着表面附近的高分子的热力学和动力学 性质 我们用Monte Carlo 方法模拟了高分子在表面的临界吸附现象 给出了临界吸附点的表征方法 研究 了临界吸附点附近高分子的热力学和动力学性质 我们这里汇报三个主要研究结果 利用高分子临界 吸附的有限尺寸标度方法研究临界吸附点和临界指数 为估算临界吸附点提供了新方法[] 2 在两块平行 ν 吸附板中的高分子的临界吸附与板的间距D有关 当D > bn 时 高分子的临界吸附点与单平面的吸附相同 但临界指数不同 当D < bnν 时 高分子的临界吸附不容易观察到 但我们发现低温时 高分子只吸附在一 个平面上 且高分子仍然作正常的扩散[2] 3 吸附的高分子的动力学平动扩散和转动驰豫过程发生变化 扩散系数D和驰豫时间 R的变化与表面的吸附能EPS和高分子链内的吸引能EPP有关 见图 同样标度关系 D ~ N 和 R ~ N 的标度指数 和 也与高分子链的吸附状态有关[3] Fig. Sketch of polymer states and the dependence of diffusion coefficient D and rotational relaxation time R on the intra-polymer attraction EPP and the polymer-surface attractions EPS. 关键词 高分子 临界吸附 扩散系数 驰豫时间 计算机模拟 参考文献 [] Luo, M. B. J. Chem. Phys. 2008, 28: 04492. [2] Li, H.; Qian, C. J.; Wang, C.; Luo, M. B. Phys. Rev. E 203, 87: 02602. [3] Yang, Q. H.; Luo, M. B. Sci. Rep. 206, 6: 3756. 08

I-3-22 Role of Salt and Water in PSS/PDAC polyelectrolyte complex plasticization Ran Zhang, Yanpu Zhang 2, Jodie L. Lutkenhaus 2, *, Maria Sammalkorpi 3, * State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 30022, P. R. China 2 Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas 77843, United States 3 Department of Chemistry, Aalto University, P.O. Box 600, 00076 Aalto, Finland *jodie.lutkenhaus@tamu.edu *maria.sammalkorpi@aalto.fi We investigate the plasticizing effect of salt and water on hydrated polyelectrolyte assemblies via molecular dynamics simulations corroborated by connected by experimental modulated differential scanning calorimetry (MDSC) characterization of complexes formed by poly(sodium 4-styrenesulfonate) (PSS) and poly(diallyldimethylammonium chloride) (PDAC) under varying hydration and excess salt (NaCl) conditions. The simulations reveal that while water has a definitive plasticizing effect on the polyelectrolyte complex, salt ions result in a double-faced effect. Although the presence of salt ions provides additional volume for chain motion and reduces PSS-PDAC ion pairing due to electrostatic screening which both contribute toward plastification of the complex, salt ions also bind water in their hydration shells. This results in a decrease of water mobility in the system reducing the plastification resulting from the hydration. [] Our MDSC results connect the findings to macroscopic PE plastification. The dual mechanism of salt on the PE complex properties, although quite logical, has not been previously reported or characterized as the effect is often masked in experiments because the addition of salt typically changes also the hydration in these hydrated systems. The findings bear fundamental significance in understanding hydrated polyelectrolyte assemblies and provide a direct means to tailor the mechanical characteristics of PE assemblies via interplay of water and salt. Keywords: polyelectrolyte assemblies, plastification, glass transition, molecular dynamics References:. Zhang, R.; Zhang, Y.; Antila, H. S.; Lutkenhaus, J. L.; Sammalkorpi, M., Journal of Physical Chemistry B 207, 2, 322-333. 09

I-3-23 Polymer Crystallization Induced by Nanoparticles with Different Dimensions Yijing Nie *, Zhiping Zhou Institute of Polymer Materials, Jiangsu University, 30 Xuefu Road, City, 2203 *Email: nieyijing@ujs.edu.cn Nowadays, in order to obtain polymer nanocomposites with high performance, researchers are devoted to the preparation of polymer materials in which crystalline morphology can be controlled directly. Before the realization of precise tailoring of crystalline structure in polymer nanocomposites, the microscopic mechanism of polymer crystallization induced by nanoparticles with different dimensions should be first understood. The presence of nanoparticles with different dimensions can result in the changes of polymer crystallization behaviors. Herein, dynamic Monte Carlo simulations were used to study the microscopic mechanism of the effects of filler dimension on polymer crystallization. It was found that polymer crystallization kinetics, crystal growth dimension and crystal orientation are all influenced by filler dimension. The system with the one-dimensional nanoparticle exhibits the strongest crystallizability due to the largest surface area, the highest segmental orientations of chain segments and the highest segment density in interfacial regions. The zero-dimensional nanoparticle has the weakest ability to induce polymer crystallization attributed to the smallest surface area, the lowest segmental orientations of chain segments and the lowest segment density in interfacial regions. The system with the two-dimensional nanoparticle has the smaller surface area, the lower segmental orientations and the lower segment density in interfacial regions compared with that with the one-dimensional nanoparticle, and thus it exhibits the weaker crystallizability than that with the one-dimensional nanofiller but the higher crystallizability than that with the zero-dimensional nanofiller. These simulation results successfully reveal the underlying microscopic mechanism of the effects of filler dimension on polymer crystallization, and can provide some new information for the design and tailoring of crystalline polymer nanocomposites. Fig. Snapshots of polymer crystalline morphologies in the systems with zero-dimensional nanoparticle (the left one), one-dimensional nanoparticle (the middle one) and two-dimensional nanoparticle (the right one), respectively. Keywords: polymer crystallization; Monte Carlo simulations; nanoparticle; filler dimension References: [] Ning, N.; Fu, S.; Zhang, W.; Chen, F.; Wang K.; Deng H.; Zhang Q,; Fu, Q. Prog. Polym. Sci. 202, 37: 425. [2] Yang, J.; Yang, C.; Wang, M.; Chen, B.; Ma, X. Phys. Chem. Chem. Phys. 20, 3: 5476. [3] Nie, Y.; Zhang, R.; Zheng, K.; Zhou, Z. Polymer 205, 76:. 0

I-3-24 偶氮高分子体系响应性质的理论研究 张兴华 北京交通大学, 北京市海淀区上园村 3 号,00044 *Email: zhangxh@bjtu.edu.cn 刺激 - 响应材料的形态 尺寸或模量敏感地依赖与环境中光 热 电 磁等物理性质 这类材料使软物质体系的功能化 器件化化成为可能 与其他刺激 - 响应材料相比, 光响应材料具有无需导线 电极等能量和信号输入机构, 可以实现远程的操控, 并容易制成柔性器件等优点, 是这一领域关注的焦点 材料对光信号的响应性质一般是通过引入具有光致异构特性的偶氮苯集团来实现的 这一集团具有顺式和反式两种构象状态, 在光照条件的改变来实现两种状态间的转变 这两种构象状态要求偶氮键的键角取特定的角度, 这需要在描述高分子链统计的配分函数中引入对键角的约束 采用传统的自洽场理论研究这一系统时需要对偶氮键两端的 tail 和 spacer 嵌段 分别求解传播子 qtail 和 qspacer, 并通过如下公式来约束周线变量 s=sazo 两端的传播子, 以保证偶氮键的键角 azo, q spacer r, u, sazo qtail r, u ', sazo asin u u ' azo du ' 这大大提高了自洽场理论计算的难度, 在保证精度需要情况下, 计算量的负担数十倍提升 我们采用路径积分的观点来代替扩散方程的求解, 即在辅助场中的蒙特卡洛的方法对高分子构象的采样来获得系综平均 这样对偶氮键键角的约束, 只需在蒙特卡洛尝试移动中保持偶氮键的键角不变即可 在蒙特卡洛求解路径积分的过程当中, 随着自由度数目的增多, 要求更多蒙特卡洛步来保证积分的遍历性 ; 而限制了给定键的角度的偶氮高分子体系相当于自由度的降低, 因而在给定精度的条件下, 反而提高了计算效率 采用这一理论方案我们开展了系列的偶氮高分子体系响应性质的研究 本文简述光响应的高分子刷及其应用 光控高分子刷高度的变化是来自于链的折叠状态和伸展状态的竞争 在一定接枝密度以上可以形成这两种状态的双稳定态 通过接枝密度的调整可以控制两个状态的概率 在双稳定态的情况下高分子链的光控折叠过程是一个一级转变过程, 两种状态之间的转变需要能耗, 此时光照条件下形成的塌缩状态是热力学稳定的结构 将这一光控高分子刷接枝于纳米球表面可以实现光控尺寸可变的纳米颗粒 整个纳米颗粒的尺寸由球状衬底的尺寸和高分子刷的高度来共同决定 在无光照条件下, 接枝的高分子链处于伸展构象, 颗粒处于大尺寸状态 ; 在光照条件下, 高分子链由于偶氮苯集团光致异构的作用促使高分子刷高度的降低, 从而导致整个球状颗粒的尺寸的降低 这一体系的光响应性质由三个特征长度尺度来控制 : 高分子的链长 L 从高分子的接枝点到偶氮键的链段 (Spacer) 的长度 高分子链上能够受到偶氮键集团控制的部分 (tail) 的长度 tail 和 spacer 两个链段的长度不是完全独立的, 更重要的是他们的匹配程度 关键词 : 偶氮高分子 ; 光响应 ; 高分子刷 ; 单链平均场理论 ; 蠕虫链模型 参考文献 [] Fu, J.; Zhang, X. H.; Miao, B.; Yan, D. D. J. Chem. Phys. 207, 46: 6490.

I-3-25 高分子 / 纳米粒子复合材料动力学性质的计算机模拟 钱虎军 *, 陈弢, 吕中元 超分子结构与材料国家重点实验室, 理论化学研究所, 吉林大学, 吉林省长春市前进大街 2699 号, 邮编 3002 *Email: hjqian@jlu.edu.cn 通过纳米粒子掺杂是实现高分子材料性能优化的常见手段 [] 理解此类复合体系中各类纳米粒子的加入对复合物动力学性质的影响机制及规律至关重要, 例如对高分子材料熔融态下粘度的调控 [2] 必将影响材料的加工性能 近期, 我们通过计算机模拟研究发现, 如果将少量由高分子单链通过链内交联获得的单链交联软纳米粒子加入到聚合物熔体中, 纳米粒子与熔体链之间体现出了典型的液 / 液界面特性, 这与无机粒子体系中的固 / 液界面形成了鲜明的对比 而这种良好的界面结合能力和软纳米粒子固有的表面形变能力为界面处的熔体链段带来了明显的界面加速效应 [3] 同时我们发现, 随着熔体链聚合度 N 的增加, 在短链熔体中, 纳米粒子的扩散能力随着 N 的增加而线性下降, 符合传统 Stokes-Einstein 方程 而在缠结体系中,N 的变化不再影响纳米粒子的扩散, 其扩散速率随着 N 的增加并不改变 我们的模拟表明 : 在缠结体系中, 随着纳米粒子的快速扩散, 在多次碰撞及局部加速的协同作用下, 熔体链的松弛将得到多级加速, 最终导致熔体链的松弛不仅存在明显的加速效应而且加速效果随着链长的增加而逐级放大 同时, 复合物中熔体链的松弛时间与链长之间存在着与纯聚合物熔体中完全不同的标度规律 这些结果不仅为相关高分子材料加工条件的优化与设计提供了理论参考, 也为传统高分子理论的发展提出了新的思路与挑战 Figure. (a) A schematic view of the simulated composite where SCNPs (drawn in red) are dispersed in a linear chain melt (in cyan); (b) Accelerated relaxation of the melt chains in composites. 关键词 : 高分子 / 纳米粒子复合物 ; 单链交联软纳米粒子 ; 动力学性质 ; 粘度下降 ; 分子动力学模拟 参考文献 [] Green P. F. Soft Matter 20, 7: 794. [2] Mackay M. E.; Dao T.; Tuteja A.; Ho D. L.; van Horn B.; Kim H.; Hawker C. J. Nat. Mater. 2003, 2: 762. [3] Chen T.; Qian H.-J.; Zhu Y.-L.; Lu Z.-Y. Macromolecules 205, 48, 275. 2

I-3-26 碳材料相关的理论模拟研究 李剑锋 *, 张红东, 邱枫, 杨玉良 复旦大学高分子科学系, 上海市邯郸路 220 号, 邮编 200433 *Email: lijf@fudan.edu.cn 本报告总结了作者近几年在碳材料相关领域的理论模拟研究工作, 着重探讨如何将理论与实验和工业生产有机地结合起来 首先运用曲面形变理论结合材料力学解释了碳纳米管纤维膜通电收缩机理, 并通过模拟计算解释了此类碳材料的各类形变响应问题, 为精细化开发新型多功能碳材料提供了理论支持 其次结合试验, 研究了碳纤维生产工艺中的氧化炭化过程, 提出了柱面并联下的耦合双化学反应的拉伸流变学模型, 并通过模拟计算得到了优化的工艺参数并已成功地应用于生产实践中 关键词 : 碳纤维 ; 碳纳米管纤维 ; 流变学参考文献 [] Chen, P.N.; Xu, Y.F.; He, S.S.; Sun, X.M.; Guo, W.H.; Zhang, Z.T.; Qiu, L.B.; Li, J.F.; Chen,D.Y.; Peng, H. S. Adv. Mater. 205, 27: 042. [2] Deng, J.; Li, J.F.; Chen, P.N. et al. J. Am. Chem. Soc. 206, 38: 225 3

I-3-27 嵌段共聚物三维软受限自组装的实验与模拟研究 朱雨田 *, 闫南, 盛玉萍, 姜伟 中国科学院长春应用化学研究所, 高分子物理与化学国家重点实验室, 长春市人民大街 5625 号, 邮编 30022 *Email: ytzhu@ciac.ac.cn 将嵌段共聚物引入受限空间内进行自组装, 由于受限效应与模板效应, 嵌段共聚物可以自组装形成一些开放体现不能获得的新颖组装结构 [] 在本工作中, 我们通过实验和 Monte Carlo 模拟相结合, 研究了嵌段共聚物在三维乳液软受限条件下的自组装及其与无机功能纳米粒子的受限共组装 实验和模拟不仅发现了众多新颖自组装结构, 同时还揭示了自组装过程中熵效应和焓效应对组装结构及无机纳米粒子排列分布的影响规律, 如图 所示 : Fig. Self-assembled structures of block copolymer and gold nanoparticles confined in emulsion droplets. 关键词 : 嵌段共聚物 ; 自组装 ; 纳米粒子 ; 三维软受限参考文献 [] He, X. H.; Song, M.; Liang, H. J.; Pan, C. Y. J. Chem. Phys. 200, 4: 050. 4

I-3-28 非活性残基对酶催化反应能力的影响 周燕子 *, 雷金平, 魏婉清, 谢代前, 张颖凯 2 南京大学, 化学化工学院, 理论与计算化学研究所, 南京, 20023 2 纽约大学化学系, 纽约, 美国,0003 *Email: zhouyz@nju.edu.cn 酶催化反应的速率不仅受活性中心的控制, 也受到复杂的酶环境的影响 多肽药物通常容易被蛋白酶水解, 提高多肽药物的抗水解性非常重要 丝氨酸酶可以水解多肽 MCTI-A 及其变异体, 底物相似, 活性中心相同, 反应机理一样, 但水机反应速度却相差上万倍 阿司匹林可以通过酰化 Ser530 的羟基来抑制环氧合酶 COX- 和 COX-2, 但它抑制 COX- 比抑制 COX-2 更强, 将产生消化性溃疡和消化不良等副作用 然而阿司匹林在整个药物市场都占有很大的比例, 所以寻找阿司匹林的替代物是近年来的重要课题之一 我们采用 Born-Oppenheimer 从头算量子力学 / 分子力学动力学模拟方法 (QM/MM-MD) 研究了丝氨酸酶可以水解多肽 MCTI-A 及其变异体的机理以及阿司匹林抑制环氧合酶的具体机理 发现了影响酶反应速率的位于活性中心之外的重要氨基酸残基, 为设计抗水解的多肽药物以及 COX-2 高选择性的类阿司匹林药物提供了理论依据 Figure. Overlap of the structures of COX- and COX-2 at EI state. The carbon atoms are colored green in COX-, while cyan in COX-2. Contributions from some important residues to stabilization the transition state are also labeled in red for COX- (in kcal/mol), and in blue for COX-2. The negative value indicates that the residue helps to decrease the activation barrier, whereas the positive one indicates that the residue would deter the reaction. 关键词 : 共价抑制剂 ; 药物选择性 ; 丝氨酸蛋白酶 ; 量子力学 / 分子力学动力学模拟 参考文献 [] Gierse, J. K.; Koboldt, C. M.; Walker, M. C.; Seibert, K.; Isakson, P. C. Biochem. J. 999, 339: 607 [2] Mitchell, J. A.; Akarasereenont, P.; Thiemermann, C.; Flower, R. J.; Vane, J. R. Proc. Natl. Acad. Sci. U.S.A. 993, 90: 693. [3] Kim, J. W.; Cochran, F. V.; Cochran, J. R. J. Am. Chem. Soc. 205, 37, 6-9. [4] Jinping Lei, Yanzi Zhou, Daiqian Xie, and Yingkai Zhang, J. Am. Chem. Soc., 205, 37, 70. [5] Yanzi Zhou, Daiqian Xie, and YingkaiZhang,J. Phys. Chem. Lett, 206, 7, 38. 5

I-3-29 带电高分子刷性质及其应用的理论研究 杨爽 *, 雷震, 陈尔强 北京大学化学与分子工程学院, 北京,0087 *Email: shuangyang@pku.edu.cn 将高分子一端浓密地接枝到表面或界面时形成高分子刷, 由于其在表面润滑 胶体粒子稳定性 膜表面修饰 药物释放等方面具有广泛的应用前景, 在实验及理论方面对高分子刷性质进行了大量的研究 而当高分子链单元带上电荷时, 所形成的聚电解质刷在长程静电作用力下表现出复杂的行为 我们通过高分子的自洽场理论, 强拉伸近似及计算机模拟等技术, 对带电高分子刷的各类性质做了详细深入的研究 具体地, 我们考察了带电刷的结构特点 刷诱导的膜刚性 柱状聚电解质刷的 Manning 凝聚现象及多价态盐离子诱导球状聚电解质刷的表面分离, 以及其他重要的调控因素如接枝密度 盐浓度等的影响 通过对这些带电刷的不同性质及变化规律的研究, 我们揭示出聚电解质刷内各种相互作用竞争的特点, 并为实验提供了一定的指导 关键词 : 聚电解质刷 ; 膜弹性 ; 自洽场理论 ; 强关联效应参考文献 [] Lei, Z.; Yang, S. *; Chen*, E.-Q. Soft Matter, 205,, 376 [2] Lei, Z.; Miao, B.; Yang, S. *; Chen, E.-Q. * Phys. Rev. E, 205, 9, 062602 [3] Hao, Q.-H.; Xia, G..;Tan, H.-G.; Chen, E.-Q.; Yang, S. * To be submitted` 6

I-3-30 Insights into the endosomal escape mechanism via investigation of dendrimer membrane interactions Wen-de Tian * Center for Soft Condensed Matter Physics and Interdisciplinary Research, Soochow University, Suzhou 25006, China *Email: tianwende@suda.edu.cn Understanding the mechanism of the escape of non-viral vectors from endosomes is critically important for the development of new gene delivery systems. Coarse-grained molecular dynamics simulations of responsive dendrimers interacting with tensionless and tense lipid membranes were performed to give insight into the gene escape mechanism. It was found that the insertion of a charged dendrimer into a membrane is facilitated by the asymmetric distribution of charged lipids and the strongly charged dendrimer can cause a breakdown of membrane asymmetry. Furthermore, dendrimer adsorption could lead to the drop of critical stress required to disrupt the membrane. We propose that a fundamental way for nanoparticles to penetrate through targeted membranes is endowing them with capabilities to tune the local membrane tension. Finally, an escape mechanism of delivered gene materials from an endosome was suggested: a cooperation between global effect, resulting from osmotic pressure and the increase of dendrimer size in the endosome, and local effects caused by the electrostatic adsorption of dendrimers. Fig. A possible mechanism of endosomal escape of dendrimers Keywords: dendrimer, endosomal escape, computer simulation References: [] W-d Tian, Y-q Ma Soft Matter, 202,8, 6378-6384 7

I-3-3 基于软补丁粒子体系的超胶体结构设计与调控 李占伟, 朱有亮, 吕中元 2, 孙昭艳 * 中国科学院长春应用化学研究所, 高分子物理与化学国家重点实验室, 长春 30022 2 吉林大学理论化学研究所, 超分子结构与材料国家重点实验室, 长春 30023 *E-mail: zysun@ciac.ac.cn 如何合理设计并构筑具有特殊功能的纳米结构始终是材料科学研究的核心目标之一 具有表面各向异性特性的补丁粒子 (patchy particle) 的出现给材料科学领域带来了一场令人难以置信的革命 [] 由于同时具有软形变和表面各向异性特性, 基于聚合物制备得到的软补丁胶体粒子表现出了比硬补丁粒子更丰富的聚集行为 但是, 由于软补丁胶体粒子本身结构和聚集行为的复杂性, 人们对于如何合理利用软补丁胶体粒子自组装构筑各种新颖的超胶体结构仍不清楚 因此, 设计并利用实验上简单易行的软补丁胶体粒子构筑新颖的超胶体结构, 明晰不同超胶体结构的设计原则与调控规律具有重要的理论和实际意义 我们针对各种具有各向异性特性的软补丁聚合物胶体体系, 发展了一系列简单有效的 普适性的模拟模型及方法 [2-6], 开发了相应的 GPU 加速各向异性聚合物胶体模拟模块, 为各向异性聚合物胶体体系聚集行为研究提供了一套切实可行的模拟方案 同时, 借助仿生和仿原子设计理念, 我们利用软补丁胶体粒子自组装, 研究了各种超胶体仿生螺旋结构以及非紧密堆积结构的的设计规律 热力学调控因素以及动力学形成机理 [2-6], 揭示了基于软补丁胶体粒子自组装构筑各种新颖超胶体结构的设计原则与调控机制, 为设计和开发新型功能材料提供了可靠的理论帮助 关键词 : 软补丁粒子 ; 自组装 ; 超胶体结构 ; 计算机模拟参考文献 [] S. C. Glotzer, M. J. Solomon, Nat. Mater., 6, 557, 2007. [2] Z.-W. Li, Z.-Y. Lu, Z.-Y. Sun, L.-J. An, Soft Matter, 8, 6693, 202. [3] Z.-W. Li, Z.-Y. Lu, Z.-Y. Sun, Soft Matter, 0, 5472, 204. [4] Z.-W. Li, Y.-L. Zhu, Z.-Y. Lu, Z.-Y. Sun, Soft Matter, 2, 74, 206. [5] Q.-Z. Zou, Z.-W. Li, Z.-Y. Lu, Z.-Y. Sun, Nanoscale, 8, 4070, 206. [6] Z.-W. Li, Y.-L. Zhu, Z.-Y. Lu, Z.-Y. Sun, Phys. Chem. Chem. Phys., 8, 32534, 206. 8

I-3-32 短链聚合物体系相行为的理论研究 蒋滢 *, 陈征宇 2* 北航化学与环境学院 & 软物质物理应用研究中心, 北京,009 2 加拿大滑铁卢大学, 加拿大滑铁卢,N2L 3G *Email: yjiang@buaa.edu.cn;jeffchen@uwaterloo.ca. 具有较低分子量的短链嵌段共聚物, 能够自组装形成较小尺寸的微相结构, 近年来逐渐被应用于为获得尺寸在 20nm 以下微相结构的平板印刷术 (lithography) 研究中 短链聚合物的链构象已经无法再采用柔性高斯链模型描述, 而需要运用半刚性的蠕虫状链模型来描述 对比于长链嵌段共聚物, 短链高分子的聚合度 N 与 Flory-Huggins 相互作用参数 是相互独立的变量 由于短链具有较小的链构象熵, 因此会在更低的 值处发生相分离, 同时, 随着聚合物的 N 变小, 链段单体的体积效应也会在体系发生相分离时产生重要影响 此外, 短链聚合物分子之间也存在与方向有关的相互作用, 从而体系也易形成取向特定的液晶相结构, 致使体系同时发生空间位置和取向排列的复杂相行为 我们采用基于蠕虫状链的自洽平均场方法, 并结合 random-phase-approximation 理论方法, 研究了短链嵌段共聚物自组装相行为 研究关注于短链构象熵变化和不同组分链段间相互作用的有限力程耦合作用下, 对相分离微相结构物理性质的影响 同时, 在体系中考虑与取向相关的相互作用势, 研究聚合物体系发生液晶相转变的物理机制 关键词 : 聚合物链 ; 自洽场 ; 蠕虫状链 ; 液晶相 参考文献 Jiang, Y.; Zhang, X.-H., Miao, B.; Yan, D.-D.; Chen, J. Z. Y. Microphase separation of short wormlike diblock copolymers with a finite interaction range, Soft Matter. 206, 2: 248. 2 Greco, C., Jiang, Y.; Chen, J. Z. Y., Kremer K., Daoulas, K. Maier-Saupe model of polymer nematics: Comparing free energies calculated with Self Consistent Field theory and Monte Carlo simulations, J. Chem. Phys. 206, 45: 8490. 3 Jiang, Y.; Greco, C., Daoulas, K; Chen, J. Z. Y. Thermodynamics of a Compressible Maier-Saupe Model Based on the Self-Consistent Field Theory of Wormlike Polymer, Polymers 207, 9: 48. 9

I-3-33 链的拓扑结构对嵌段共聚物自组装行为的影响 尹玉华 *, 宋永兵, 李宝会 南开大学物理科学学院, 天津市南开区卫津路 94 号,30007 *Email: yinyh@nankai.edu.cn 由于聚合物合成技术的快速发展, 对基于环形拓扑结构的高分子材料特殊性质的研究越来越受到人们的重视 相对于大家所熟知的线形聚合物和支化聚合物而言, 首尾相连的环形聚合物因为不具有外部自由端点, 显示出独特的物理性质 [] 由于环形聚合物的拓扑效应在聚集态中会被进一步放大, 在嵌段共聚物自组装体系中拓扑结构对聚合物的行为会产生更加明显的影响 [] 我们对具有相同组分的环形和线形 AB 两嵌段以及线形 ABA 三嵌段共聚物在选择性溶剂中的自组装行为进行了 Monte Carlo 模拟研究 研究结果表明, 环形嵌段共聚物体系中形成的球形胶束具有更加紧密的疏水核和亲水壳层 ; 形成的囊泡结构则具有较薄而致密的疏水壁和较大的含水核 ; 除了通常的具有单个含水室的囊泡结构以外, 我们还观察到了较宽参数区域的具有多个含水室的囊泡结构, 并且通过调节疏溶剂嵌段与溶剂的相互作用可以改变囊泡内含水室的数目 由于多室囊泡可以在单个不同的空间内存储不相容的活性物质和具有不同功能的组分, 从而避免交叉污染, 对于多室囊泡的结构特征及形成条件的研究其在化学 生物及药物运输方面的应用都具有重要意义 我们希望通过对于具有不同链结构的嵌段共聚物自组装行为的研究, 加深对于结构 - 性能关系的了解, 从而促进开发基于环状聚合物的多功能新型材料 关键词 : 环形嵌段共聚物 ; 拓扑结构 ; 自组装 ; 分子模拟参考文献 [] Endo K. Advances in Polymer Science, 2008, 27: 2-83. [2] Yamamoto T. and Tezuka Y. Soft matter, 205, : 7458-7468. 20

I-4-0 Computational Simulation and Molecular Design of Organic Electrode Materials for Li Ion Batteries Zhen Zhou * Computational Centre for Molecular Science, School of Materials Science and Engineering, National Institute for Advanced Materials, Nankai University, Tianjin 300350, China [2] *Email: zhouzhen@nankai.edu.cn The use of organic molecules as electrode materials for lithium ion batteries not only improves the capacity, but also enables the production of electrode materials with renewable raw materials. However, the voltage of the organic molecules are generally low, so increasing the voltage of organic electrode materials is critical to increase its energy density. We studied the correlation between the electron delocalization (aromaticity) and the Li-intercalation voltage of carbonyl-containing polycyclic aromatic hydrocarbons by density functional theory. Our analyses show that this correlation can be well explained by Clar s theory. In order to characterize the change in aromaticity during intercalation, we introduced the index of ΔC2Li. Guided by this theory, we have designed several molecules with good ΔC2Li values and high voltages. We have also experimentally studied the molecules with positive ΔC2Li. Our results demonstrate the importance and feasibility of Clar's theory in screening and developing high voltage organic electrode materials []. In order to improve the structural stability and cyclic capability of organic electrodes, we designed and prepared two new chemically stable naphthalimide-based crystalline covalent organic frameworks (COFs), and excellent electrochemical performances were achieved as cathode materials for Li-ion batteries [2]. Fig. Voltage variation with ΔC2Li. Keywords: Li ion batteries; organic electrode materials; aromaticity; stability; covalent organic frameworks References: [] Wu, D.H.; Xie, Z.J.; Zhou, Z.; Shen, P.W.; Chen, Z.F. J. Mater. Chem. A 205, 3: 937. [2] Yang, D.-H.; Yao, Z.-Q.; Wu, D.H.; Zhang, Y.H.; Zhou, Z.; Bu, X.-H. J. Mater. Chem. A 206 4, 862. 2

I-4-02 精确范德华分子力场及其应用邓伟侨中国科学院大连化学物理研究所, 大连 6023 Email: dengwq@dicp.ac.cn Abstract 范德华作用力是分子间基本作用力之一, 在各个化学领域起着至关重要的作用, 比如孔隙和表面吸附与催化等 我们开发了一套精确范德华分子力场, 可以精确描述多孔材料与气体分子间的范德华相互作用, 因此可以用来模拟多孔材料对小分子的吸附情况 我们应用了这一精确范德华分子力场, 来设计多种纳米孔材料 设计了储氢材料 CO2 捕获与转化微孔高分子以及水处理微孔高分子, 并在实验上合成并验证了相应设计的多孔材料, 得到较好性能的新型材料 Reference: 图. 模拟与设计氟代共轭微孔高分子过程. Y. Xie,T.T. Wang,X.H. Liu, K. Zou, W.Q. Deng Nature Commun., 203, 4, 960. 2. R.X. Yang, T.T. Wang, W.Q. Deng Sci. Rep.,205, 5, 055. 22

I-4-03 Striped patterns self-assembled from rod-coil diblock copolymers on spherical substrates Jiaping Lin * School of Materials Science and Engineering, East China University of Science and Technology, Meilong Road 30, Shanghai, 200237 *Email: jlin@ecust.edu.cn Introduction of geometric constraints in polymer systems, such as by confining block copolymers on substrates, allows for the polymers to self-assemble into novel nanostructures. In particular, the structures produced under curved constraints have attracted significant attention. In addition to the morphologies, topological defects are an important feature of the structures. However, the self-assembly mechanism and topological defects of the self-assembled structures on the substrate are still not clear. We employed dissipative particle dynamics method to study the structures self-assembled from rod-coil diblock copolymers on spherical substrates in solutions (see Fig a,b). The stripes are formed by orderly packed rod blocks that were stabilized by coil blocks in solvents (see Fig. c). Three types of disclinations with charges of +, +/2, and -/2 and dislocations were observed in the striped patterns. The sum of the disclination charges was always +2, which is consistent with the Poincaré-Hopf theorem. Two categories of local defect striped patterns were observed, that is, spiral-like and ring-like. The self-assembled structures and surface densities of defects depend on various parameters including the rigidities of the rod blocks, the radii of the spheres, and the hydrophobicities of the rod blocks. The theoretically predicted structures are further verified by experimental observations (see Fig. d). The work provides a route towards producing striped patterns on curved substrates and can serve as a theoretical support for preparing nanoparticles with complex surface structures. Fig. (a) Rod-coil diblock copolymers self-assemble on (b) spherical substrate. (c) Morphology of the striped pattern predicted by dissipative particle dynamics simulation. (d) SEM image of the wool-ball-like structures self-assembled from mixtures of poly(γ-benzyl L-glutamate)-b-poly(ethylene glycol) and polystyrene in selective solvents. The scale bar is 500 nm. Keywords: self-assembly; copolymer; defect; dissipative particle dynamics References: [] Zhang, L.; Wang, L.; Lin, J. ACS Macro Lett. 204, 3: 72. [2] Zhang, X.; Wang, L.; Zhang, L.; Lin, J.; Jiang, T. Langmuir 205, 3: 2533. [3] Zhu, X.; Guan, Z.; Lin, J.; Cai, C. Sci. Rep. 206, 6: 29796. [4] Guan, Z.; Wang, L.; Lin, J.; Zhu, X. Mater. Chem. Front. 207, : 697. 23

I-4-04 基于自适应偏置力的自由能计算方法 蔡文生 *, 付浩浩, 赵谈封, 邵学广 南开大学化学学院, 分析科学研究中心, 天津市卫津路 94 号,30007 *wscai@nankai.edu.cn 自适应偏置力方法 (adaptive biasing force, ABF) [] 是常用的自由能计算方法 但是传统 ABF 方法的实际应用会受到如下限制 :() 无法自定义反应坐标 ;(2) 体系中施加的约束需要和反应坐标正交 ;(3) 如果进行多维自由能计算, 则各个维度之间需要相互正交 上述限制极大的影响了 ABF 方法的应用范围 因此, 我们实现了扩展自适应偏置力方法 (extended ABF, eabf) [2], 该方法克服了传统 ABF 方法的限制, 并且提高了模拟的收敛速度 为了进一步提高多维自由能计算的效率, 我们将 eabf 方法与广义自适应偏置力 (generalized ABF,gABF) 方法结合, 进一步提出了扩展广义自适应偏置力方法 (extended generalized ABF, egabf) [3] gabf 方法在计算过程中忽略了反应坐标之间的耦合项, 从而实现在高维空中采样加速 但在反应坐标之间高度相关的情况下,gABF 方法得到的自由能面会偏离真实值 而 eabf 方法由于引入了一组虚拟原子, 使得与之关联的反应坐标之间的耦合程度大大减弱 因此两者的结合不仅可以极大地提高多维自由能计算的收敛速率, 而且避免了计算精度的损失 eabf 和 egabf 方法均已在知名分子动力学软件 NAMD 中实现, 有望在生物分子机器运动机理的研究中得到广泛的应用 关键词 : 自由能计算 ; 分子模拟 ; 自适应偏置力 ; 重要性采样 Figure. Free-energy landscapes for (A) the isomerization of cyclohexane and (B) the unbinding of two water molecules in the gas phase, derived from ABF and eabf simulations. The error bars correspond to the standard error inferred from ten independent 2 ns runs. Figure 2. Two-dimensional free-energy landscapes underlying the isomerization of NANMA, obtained from two 20 ns (A) gabf and (B) egabf calculations. RMSD of each PMF with respect to that by a 200 ns ABF calculation is listed under each panel. 参考文献 [] Darve E., and Andrew P. J. Chem. Phys., 200, 5: 969. [2] Fu, H., Shao, X., Chipot, C., et al. J. Chem. Theory Comput., 206, 2: 3506. [3] Zhao, T., Fu, H., Lelièvre, T., et al. J. Chem. Theory Comput., 207, 3: 566. 国家自然科学基金项目 (No. 23737) 资助 24

I-4-05 Molecular-level computer simulations on the self-assembled peptides with catalytic activity Ruiheng Song, Guixiang Zeng, Bing Xue 2, Wenfei Li 2, Yi Cao 2, Hao Dong,* & Wei Wang 2,* Kuang Yaming Honors School, Nanjing University, Nanjing, P.R. China 2 Department of Physics, Nanjing University, Nanjing, P.R. China *Email: donghao@nju.edu.cn, wangwei@nju.edu.cn Molecular self-assembly is ubiquitous in nature. Exploiting the principles of self-assembly could help people to create new materials with novel structures and functions. Amyloid fibrils made up with self-assembled short peptides have well-defined structures, which are able to form functional motif. In this work, we employed multi-scale molecular simulations to study amyloid-forming short peptides, which were reported to have remarkable activity to mimic the carbonic anhydrase. The building block is a 7-peptide with alternate hydrophobic and hydrophilic residues: the hydrophobic side-chains are able to have stable packing interactions with each others, and the hydrophilic histidine side-chains is capable of forming active sites for the catalytic reactions. Firstly, we explored the aggregation of peptides into organized structure as a consequence of hydrogen bonding and hydrophobic packing interactions among the subunits. Molecular simulations suggested that the sequence of the peptide greatly affects the pattern of the assembled structure, and therefore influences its catalytic activity. Based on the self-organized structure, we did systematic conformational searching on the rotamer library of histidine side-chain which are exposed to the solvent molecules, and identified two new coordination forms which are different from the structure in the active site of carbonic anhydrase. We further explored the atomic mechanism of the catalytic reaction taking place at the interface, compared it with the reaction happening at the active site of carbonic anhydrase, and proposed how to improve the catalytic activity of the artificial material. 25

I-4-06 禀异 双功能体系催化储氢释氢 : 仿生策略的青出于蓝柯卓锋,* 中山大学材料科学与工程学院, 广州海珠区,50275 *Email: kezhf3@mail.sysu.edu.cn 氢是一种清洁的可再生能源 通过化学键的形式储存 / 释放氢能用做绿色化学燃料, 有望帮助解决社会面临的能源危机及其环境污染问题 实现温和条件下高效的催化氢分子转化, 其关键在于新催化模式及催化剂设计 我们近期在仿生双功能催化的理论研究上取得了一定的进展, 阐明了配体作用模式, 金属中心电子态, 和多功能位点选择等影响催化剂构效关系和机理变化的系列关键因素 [] 更重要的是, 我们从传统的仿生双功能出发, 理论上拓展了一种 禀异 Lewis 酸 - 过渡金属亲电双功能的新概念 [2] 不同于传统仿生的 Lewis 碱 - 过渡金属双功能策略,Lewis 酸 - 过渡金属类新型催化剂可以巧妙利用配体的缺电子 Lewis 酸位点, 通过特异的亲电模式辅助氢负离子转移, 促进催化氢分子转化 Lewis 酸 - 过渡金属催化剂的独特反应性和催化模式, 有望为实现温和条件下可控的催化氢分子转化, 循环利用氢能提供新的途径和思路 Fig. Metal ligand cooperation strategies in bio-inspired bifunctional catalyts for hydrogen transforamtions. 关键词 : 仿生催化 ; 氢能 ; 双功能 ; 催化剂设计 ;Lewis 酸 - 过渡金属参考文献 [] (a) Hou, C., Jiang, J., Li, Y., Zhang, Z., Zhao C.*, Ke, Zhuofeng*. ACS Catal. 207, 7: 786. (b) Hou, C., Jiang J., Zhang S., Wang G., Zhang Z., Ke, Zhuofeng*, Zhao C.* ACS Catal. 204, 4: 2990. (b) Hou C., Zhang Z., Zhao, C.*, Ke Zhuofeng*. Inorg. Chem. 206, 55: 6539. (d) Hou, C., Jiang, J., Li, Y., Zhang, Z., Zhao C.*, Ke, Zhuofeng*. Dalton Trans. 205, 44: 6573 [2] (a) Li, Y., Hou, C., Jiang, J., Zhang, Z., Zhao, C., Page, A., Ke, Zhuofeng*. ACS Catal. 206, 6:655. (b) Y. Li, J. Zhang, S. Shu, Y. Shao, Y. Liu and Z. Ke, Chin. J. Org. Chem., 207. DOI: 0.6023/cjoc20703002 致谢 国家自然科学基金 (267330 & 247326). 广东省杰出青年基金 205A030306027; 26

I-4-07 表面单分子体系中的量子态的理论研究 郑晓 * 中国科学技术大学合肥微尺度物质科学国家实验室, 安徽省合肥市金寨路 96 号,230026 *Email: xz58@ustc.edu.cn 近年来, 利用扫描隧道显微镜等实验手段, 研究人员实现了对吸附在金属表面的分子 ( 如图 所示 ) 的局域自旋或电子态的精确测量与调控, 并发现了一些新奇的现象 对处于复杂材料环境中的磁性分子性质的研究, 将对单分子量子器件 量子信息与量子计算等领域有着重要意义 然而, 传统第一性原理方法无法定量描述电子的强关联效应 ; 而如何刻画复杂环境与外场对吸附分子结构与性质的影响, 也为理论方法带来了挑战 我们发展了适用于开放电子体系的级联运动方程 (HEOM) 方法, 并开发了高效 实用的数值计算程序 HEOM-QUICK HEOM 方法的优势在于 :() 可在统一的理论框架下, 精确计算量子杂质体系的多种性质 ( 包括静态和动态 平衡态和非平衡态性质 );(2) 可准确 高效的模拟局域量子态在复杂外场 ( 交变电磁场 微波场 温度梯度场 ) 调控下的动态响应, 并严格处理环境记忆效应 通过将密度泛函理论 (DFT) 与 HEOM 方法相结合, 我们实现了在第一性原理水平上, 模拟表面磁性分子中的局域自旋或关联电子态在外场 / 环境调控下的演变 DFT+HEOM 方法有望成为研究表面磁性分子中的局域量子态的常规方法 在本报告中, 我将介绍 DFT+HEOM 方法的发展 [-3], 以及一些具有代表性的应用 [4-6] Fig. Left: Top and side views of d-copc/au() adsorption complex. Right: Simulated di/dv curves by DFT+HEOM method (inset: comparison between experimental and numerical data. 关键词 : 开放电子体系 ; 表面磁性分子 ; 强关联电子态 ; 级联运动方程方法 ; 第一性原理方法参考文献 [] Jin, J. S.; Zheng, X.; Yan, Y. J. J. Chem. Phys. 2008, 28: 234703. [2] Li, Z.; Tong, N.; Zheng, X.; Wei, J. H.; Hu, J.; Yan, Y. J. Phys. Rev. Lett. 202, 09: 266403. [3] Hou, D.; Wang, S.; Wang, R.; Ye, L.; Xu, R. X.; Zheng, X.; Yan, Y. J. J. Chem. Phys. 205, 42: 042. [4] Wang, Y.; Zheng, X.; Li, B.; Yang, J. J. Chem. Phys. 204, 4: 08473. [5] Wang, X.; Hou, D.; Zheng, X.; Yan, Y. J.; J. Chem. Phys. 206, 44: 0340. [6] Wang, Y.; Zheng, X.; Yang, J. Phys. Rev. B 206, 93: 254. 27

I-4-08 体相形成柱状相的两嵌段共聚物薄膜在溶剂退火条件下 自组装行为的分子模拟研究 * 郝金龙, 李宝会 南开大学, 天津市南开区卫津路 94 号物理科学学院,30007 *Email: baohui@nankai.edu.cn 嵌段共聚物由于能够通过微相分离而形成丰富的纳米尺度的有序相结构, 已经成为软物质自组装的典 [] [2~3] 型范例 垂直形貌的嵌段共聚物薄膜在纳米刻蚀 超滤纳米薄膜等领域中有着重要应用 但是由于两嵌段共聚物的两种嵌段一般具有不同的表面能, 水平形貌更加稳定 实验上, 人们常用溶剂蒸汽退火 ( 溶 [, 2] 剂退火 ) 方法来增强嵌段共聚物薄膜的形貌有序性 调节薄膜形貌取向 溶剂增强了嵌段共聚物链的移动性, 有助于薄膜形成长程有序结构 并且, 溶剂会影响嵌段间有效相互作用 薄膜厚度 嵌段的有效体 [4] [5] 积分数 有效表面选择性等一系列参数, 通过改变薄膜内溶剂的种类和含量可以调节薄膜的形貌或取向 [2] 不仅如此, 人们发现在适当的蒸发速率下, 溶剂蒸发或溶剂蒸汽退火可以促进垂直形貌的生成 然而对于促进垂直形貌生成的机理还不是非常清楚 我们采用 Monte Carlo 模拟研究了溶剂蒸发和溶剂退火条件下两嵌段共聚物薄膜的自组装行为 溶剂的 [6] 蒸发通过随机选择薄膜自由表面处的溶剂分子, 并将之转变为气体分子来实现. 这种蒸发方式与 Rabani 等的溶剂蒸发模型中化学势 的情形一致 每次蒸发一个溶剂分子, 随后进行一定次数的尝试运动 针对以下三种情况进行了研究 :) 将薄膜中链松弛运动限制在 蒸发区 内, 蒸发区 为上表面位于薄膜自由表面, 而下表面随着蒸发的进行而逐渐向薄膜下部推移的区域 这一假设使得相分离首先出现在薄膜 [7] 自由表面附近 ( 上部 ), 并逐渐向薄膜下部延伸 2) 没有对薄膜中链松弛运动施加限制 3) 对处于无序态的薄膜进行反复溶胀 - 蒸发处理 针对每种情况, 我们考察了气体选择性 溶剂选择性 溶剂蒸发速率等因素对溶剂蒸发后薄膜形貌的影响 ; 确定了垂直柱形貌能够出现的表面选择性范围 发现垂直柱状相更易在强溶剂选择性和快速蒸发的条件下出现 并将薄膜在溶剂蒸发中不同时刻的形貌与相同厚度下非溶剂蒸发的溶液薄膜形态或平衡态薄膜形态进行对比, 研究了溶剂蒸发和溶剂退火对垂直形貌生成的影响以及垂直柱形成的机理 关键词 : 嵌段共聚物薄膜 ; 溶剂蒸发 ; 溶剂退火 ; 柱状相取向 ;Monte Carlo 参考文献 [] Jeong, S. J.; Kim, J. Y.; Kim, B. H.; Moon, H. S.; Kim, S. O. Mater Today 203, 6: 468. [2] Philip, W. A.; O Neil, B.; Rodwogin, M.; Hillmyer, M. A.; Cussler, E. L. ACS Appl Mater Interfaces 200, 2: 847. [3] Yang, S. Y.; Ryu, I.; Kim, H. Y.; Kim, J. K.; Jang, S. K.; Russell; T. P. Adv Mater 2006, 8: 709. [4] Jeong, J. W.; Park, W. I.; Kim, M. J.; Ross, C. A.; Jung, Y. S. Nano Lett 20, : 4095. [5] Cavicchi, K. A.; Russel, T. P. Macromolecules 2007, 40: 8. [6] Rabani, E.; Reichman, D. R.; Geissler, P. L.; Brus, L. E. Nature 2003, 426: 27. [7] Hao, J.; Wang, Z.; Wang, Z.; Yin, Y.; Jiang, R.; Li, B.; Wang, Q. Macromolecules 207, 50: 4384. 28

I-4-09 大分子电子结构计算方法研究 李伟 *, 黎书华 南京大学化学化工学院, 南京,2009 *Email: wli@nju.edu.cn 传统的量子化学电子结构方法由于计算标度高, 因此很难用于复杂的大分子体系 为了克服该困难, 我们发展了两类用于大分子的线性标度的电子结构方法, 基于能量的分块 (GEBF) 方法 [-2] 和分子中的簇 (CIM) 局域相关方法 [3-4] 在 GEBF 方法中, 大体系的总能量可以表示为一系列静电嵌入的子体系的能量的线性组合, 该方法最近被推广到显式相关的 F2 方法 [5] 溶液的电子吸收光谱[6] 等 使用该方法, 我们在水簇和溶液体系的能量和光谱研究中取得了一系列进展 [5,7] 在 CIM 方法中, 每个占据局域分子轨道的电子相关能贡献可以通过 簇 的计算近似获得, 这里 簇 仅包含一小部分局域分子轨道 CIM 方法近期也被用于固体表面的吸附 [8] 化学反应的多层次和杂化模型[4] Fig. The changes of hydrogen bonds in melting process of ice-ih (H2O) 64 crystal 关键词 : 大分子 ; 线性标度 ; 关键词三 ( 五号宋体, 关键词个数不超过 5 个 ) 参考文献 [] Li, W.; Li, S.; Jiang, Y. J. Phys. Chem. A 2007, : 293. [2] Li, S.; Li, W.; Ma, J. Acc. Chem. Res. 204, 47: 272. [3] Li, W.; Piecuch, P; Gour, J. R.; Li, S. J. Chem. Phys. 2009, 3: 409. [4] Li, W.; Ni, Z; Li, S. Mol. Phys., 206, 4: 447. [5] Wang K.; Li, W.; Li, S. J. Chem. Theory Comput. 204, 0: 546. [6] Li, W.; Li, Y.; Lin, R.; Li, S. J. Phys. Chem. A 206, 20: 9667. [7] Zhang, L.; Li, W.; Fang, T.; Li, S. J. Phys. Chem. A 207, 2: 4030. [8] Li, W.; Chen, C.; Zhao, D.; Li, S. Int. J. Quantum Chem. 205, 5: 64. 29

I-4-0 钙钛矿及碳硅复合等能源纳米材料的模拟 李有勇, 林海平, 王璐, 董慧龙, 纪玉金, 刘云霞 苏州大学功能纳米与软物质研究院, 苏州工业园区仁爱路 99 号,2523 *Email: yyli@suda.edu.cn http:/modeling.org.cn 有机无机杂化钙钛矿材料由于其良好的光电转化效率而被认为是下一代太阳能电池材料的有力竞争者, 并成为近期的科研热点 通过扫描隧道显微镜 (STM) 表征和第一性原理计算 STM 模拟我们得到了 []CH3NH3PbBr3 单晶在低温下的最稳定表面的高分辨图像和原子结构 CH3NH3PbBr3 单晶的最稳定表面被确定为 CH3NH3 分子和 Br 原子曝露的 (00) 重构表面 在这个表面上, 甲胺分子可以有相互垂直和相互平行两种稳定构型,CH3NH3PbBr3 单晶的最稳定表面的确定将对未来新一代太阳能电池材料的研发产生重要的指导作用 通过第一性原理计算 [2], 我们发现无缺陷的 CH3NH3PbBr3(00) 表面与常见的环境小分子 (H2O O2 等 ) 相互作用非常弱, 是一个化学性质比较稳定的结构, 发现在真空和有水环境下,CH3NH3PbBr3(00) 表面最有可能出现的缺陷结构分别是 Br 原子单空位缺陷和 Br-MA 双空位缺陷 研究发现水溶液的存在可以显著降低缺陷的形成能 在溶液环境中, 空位缺陷附近的甲胺分子会与环境中的极性分子形成较强的氢键作用, 导致缺陷附近表面原子的错位, 钙钛矿表面的卤素空位缺陷结构是钙钛矿材料发生分解的重要源头 该工作揭示了有机 / 无机混合钙钛矿材料的表面缺陷结构, 并给出了表面缺陷结构与常见环境小分子 ( 如水 氧气等 ) 的微观作用机制, 为提高有机无机钙钛矿材料的稳定性提供了理论依据和解决思路 同时我们也模拟和设计了一系列碳硅复合等能源纳米材料, 比如硅铑复合材料用于 HER 催化 [3], 碳硅复合二维纳米材料用于光电材料 [4] 等等 关键词 : 能源材料 ; 纳米材料 ; 钙钛矿材料 参考文献 [] Robin Ohmann, Luis K. Ono, Hui-Seon Kim, Haiping Lin, Michael V. Lee, Youyong Li*, Nam-Gyu Park*, Yabing Qi*, J. Am. Chem. Soc., 205, 37, 6049. (highlighted by X-Mol http://www.x-mol.com/news/863). [2] Yunxia Liu, Krisztian Palotas, Xiao Yuan, Tingjun Hou, Haiping Lin*, Youyong Li*, Shuit-Tong Lee, "Atomistic origins of surface defects in CH3NH3PbBr3 perovskite and their electronic structures", ACS Nano, 207,,2060-2065. (highlighted by XMOL: http://www.x-mol.com/news/608) [3] Lili Zhu, Haiping Lin, Youyong Li*, Fan Liao, Yeshayahu Lifshitz, Minqi Sheng, Shuit-Tong Lee*, Mingwang Shao*, "A rhodium/silicon co-electrocatalyst design concept to surpass platinum hydrogen evolution activity at high overpotentials." Nature Communication, 206, 7, 2272. [4] Huilong Dong, Liujiang Zhou*, Thomas Frauenheim, Tingjun Hou, Shuit-Tong Lee, Youyong Li*, "SiC7 siligraphene: novel donor material with extraordinary sunlight absorption", Nanoscale, 206, 8, 6994-6999. 30

I-4- Dominant Kinetic Pathways in CVD Growth of Graphene: Hydrogen Saturation Induced Edge Stabilization Zhenyu Li ( 李震宇 ) Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui 230026, China *Email: zyli@ustc.edu.cn The most popular way to produce graphene nowadays is chemical vapor deposition, where, surprisingly, H2 gas is routinely provided even though it is a byproduct itself. In this study, by identifying dominant growing pathways, we unambiguously reveal the central role hydrogen played in graphene growth. Depending on the H2 pressure, hydrogen can saturate the edges of a growing graphene island to some extent. Although graphene etching by hydrogen has been observed in experiment, hydrogen saturation actually stabilizes graphene edges by reducing the detachment rates of carbon-contained species. Such a new picture well explains some puzzling experimental observations and opens a new avenue for edge functionalization based growth protocol optimization for two-dimensional atomic crystal van der Waals epitaxy. Keywords: o growth mechanism; multiscale simulation; feeding species 3

I-4-2 复杂体系的激发态电子结构和非绝热动力学 崔刚龙 北京师范大学化学学院, 北京,00875 *Email: ganglong.cui@bnu.edu.cn 化学 生物 材料等许多领域都涉及十分复杂的光物理过程和光化学反应 [-3] 仅依靠实验研究很难弄清楚它们的微观动力学机制, 理论计算在其中起着不可代替的角色 在本报告中, 我主要介绍课题组近年来在复杂体系电子结构和非绝热动力学两个方面的工作, 包括势能面交叉结构优化算法 [4] 蓝光光受体光化学反应机理 [5] DNA 中偶氮苯发色团的光异构化 硅量子点的激发态弛豫动力学等 关键词 : 光化学 ; 激发态 ; 电子结构 ; 非绝热动力学 ; 势能面交叉参考文献 [] Xie, B.B.; Liu, X.Y.; Fang, Q.; Fang, W.H.; Cui, G.L. J. Phys. Chem. Lett. 207, 8: 09. [2] Xia, S.H.; Cui, G.L.; Fang, W.H.; Thiel, W. Angew. Chem. Int. Ed. 206, 55: 2067. [3] Wang, Y.T.; Liu, X.Y.; Cui, G.L.; Fang, W.H.; Thiel, W. Angew. Chem. Int. Ed. 206, 55: 4009. [4] Liu, X.Y.; Cui, G.L.; Fang, W.H.; Theor. Chem. Acc. 207, 36: 8. [5] Chang, X.P.; Gao, Y.J.; Fang, W.H.; Cui, G.L.; Thiel, W. Angew. Chem. Int. Ed. 207, 56: 934. 32

I-4-3 Chemically Functionalized Two-dimensional Ferroelectrics/Multiferroics: Combination of High-mobility Semiconductors and Non-volatile Memory Menghao Wu( 吴梦昊 ) *, Shuai Dong 2, Kailun Yao, Junming Liu 3 *, Xiao Cheng Zeng 4 * School of Physics and Wuhan National High Magnetic Field Center, Huazhong University of Science and Technology, Wuhan 430074, China 2 Department of Physics, Southeast University, Nanjing 289, China 3 Laboratory of Solid State Microstructures, Nanjing University, Nanjing 20093, China 4 Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588, USA *Email: wmh987@hust.edu.cn Ferroelectric semiconductors combining ferroelectricity with semiconductors remain elusive because most present-day ferroelectric materials are unsuitable for such a combination due to their wide bandgaps. Herein we show first-principles evidence towards the realization of a new class of 2D ferroelectric/multiferroic semiconductors that possess high mobility, modest bandgaps, and distinct ferroelectricity that can be exploited for developing various heterostructural devices with desired functionalities. For example, we propose applications of the 2D chemical functionalized materials as 2D ferroelectric field-effect transistors with ultrahigh on/off ratio, topological transistors with Dirac fermions switchable between holes and electrons, ferroelectric junctions with ultrahigh electro-resistance, and multiferroic junctions for controlling spin by electric fields. All these heterostructural devices take advantage of the combination of high-mobility semiconductors with fast writing and non-destructive reading capability of non-volatile memory, thereby holding great potential for the development of future multifunctional devices. Keywords: 2D ferroelectricity; multiferroics; DFT calculations; graphene; phosphorene References: [] Nano Lett., 206, 6, 7309. [2] Nano Lett. 206, 6, 3226 [3] ACS Nano 207,, 6382 [4] J. Phys. Chem. Lett. 207, 8, 973 [5] Phys. Rev. B 203, 87, 08406 (R) [6] J. Am. Chem. Soc. 202, 34, 4423 [7] J. Am. Chem. Soc. 207 ASAP. 33

I-4-4 新颖二维材料的设计与模拟 李亚飞 南京师范大学化学与材料科学学院, 南京市文苑路 号,20023 *Email: liyafei@gmail.com 材料的性质与其结构息息相关, 具有新奇结构的材料往往能呈现出一些独特的性质 材料的结构本质上反应的是组成材料的原子之间的成键方式, 因此设计含有反常规化学键的低维纳米材料有望带来新的性质和应用 近年来我们通过多尺度理论计算与模拟, 设计了几种含有反常规化学键的新颖二维纳米材料, 如含有准平面五配位 C 原子的 Be5C2 单层材料 含有准平面六配位 C 原子的 Be2C 单层材料 2 含有平面四配位 C 原子的 Al2C 单层材料 3 4 含有平面四配位 Si 原子的 SiC2 单层材料和二维 GeP3 材料 5 我们详细研究了这些新颖二维材料的电子学性质, 通过多种理论手段验证了这些材料的稳定性并提出了这些材料的合成路径 这些研究不仅丰富了我们对于化学键的认识, 也为未来的纳米电子学提供了更多选择 关键词 : 二维材料, 新颖化学键, 密度泛函计算参考文献 [] Wang, Y.; Li, F.; Li, Y.; Chen, Z. Nat. Commun. 206, 7: 488. [2] Li, Y.; Liao, Y; Chen, Z. Angew. Chem. Int. Ed. 204, 53: 7248. [3] Li, Y.; Liao, Y.; Schleyer, P. v. R.; Chen, Z. Nanoscale 204, 6: 0784. [4] Li, Y.; Li, F.; Zhou, Z.; Chen, Z. J. Am. Chem. Soc. 20, 33: 900. [5] Jing, Y.; Ma, Y.; Li, Y. Heine, T. Nano. Lett. 207, 7: 833. 34

I-4-5 Electron and Energy Transfer Theory in Visible-Light Photocatalysis Xuebo Chen * * Key Laboratory of Theoretical and Computational Photochemistry of Ministry of Education, Department of Chemistry Beijing Normal University Xin-wai-da-jie No. 9, Beijing 00875. *Email: xuebochen@bnu.edu.cn Photocatalysis reactions rely on photo-induced single-electron transfer (SET) and inter-molecular energy transfer to drive the unique photochemical reactions, producing the open shell intermediates and achieving a high enantioselectivity. Accurate electronic structure calculations at the multiconfiguration perturbation theory together with the numerical simulation methods for the rate of electron and energy transfer have been employed to provide new insights into the photocatalytic cycle initiation, activation, and deactivation in the series of photocatalysis reactions mediated by chiral Lewis acid and/or photocatalysts (i.e., Ir and Ru complexes). The energy regulatory theory of excited states for the substrate-lewis acid catalyst complexes was established to account for the mechanistic discrepancy between the background and photo-catalyzed reactions. The enantioselective reaction is predominantly controlled through an enhanced spin orbit coupling, caused by relativistic effects resulting from heavy atoms in the chiral Lewis acid catalyst. As a practical photocatalysis strategy, the photocatalysts function as the effective photosensitizer to transfer their excitation energies to the substrate, producing various radical intermediates. We attempted to build the evaluation strategy for the photocatalytic efficiency based on the theoretical models of the photo-initiated electron and energy transfer that can be obtained by calculating the minimum energy profiles of the photocatalytic cycle. Keywords: Photoredox catalysis; Electron and Energy Transfer; Energy Regulatory; Photosensitization References: []Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 203, 3: 5322. [2] Wang, H. J.; Cao, X. Y.; Chen, X. B.; Fang, W. H.; Dolg, M. Angew. Chem. Int. Ed. 205, 54: 4295. [3] Han, J.; Chen, X.B. J. Mater. Chem. C, 203, : 4227. [4]Wang, H. J.; Fang, W. H.; Chen, X. B.; J. Org. Chem. 206, 8: 7093. 35

I-4-6 稠环倍半萜类天然产物生源机制的理论研究 巫瑞波 * 中山大学, 广州大学城中山大学药学院, 邮编 :5006 *Email: wurb3@mail.sysu.edu.cn 萜类天然产物是药物分子的重要来源之一 在丰富萜类及其衍生物的化学多样性方面, 时兴的生物合成较之传统的化学合成颇具优势, 然而生物合成方案的设计往往存在重现率低的缺点, 这主要是因为对萜类生源途径中相关酶催化机理的认知不够透彻 本课题组长期以来主要借助 DFT/MM MD 模拟, 系统地阐明了 ATAS TEAS 和 FSPS 等一系列稠环倍半萜类合成酶酶催化反应专一性和杂泛性 (promiscuity) 的分子机制, 揭示了调控酶催化主副反应化学选择性的热动力学因素和关键残基, 并辅以酶突变实验验证 为后续开展蛋白活性重设计 构建基于廉价工程菌的生物合成方案, 以高效地获得骨架特殊且有潜在药效的稠环倍半萜分子, 提供了重要的理论依据 Fig. Chemo- and Stereo-selectivity controlled by substrate folding mode in FSTS 关键词 : 天然产物 ;QM/MM 多尺度模拟 ; 酶催化 ; 分子模拟 MD 参考文献 [] Wang, Y.; Xie, H.; Zhou, J.; Zhang F.; Wu, R. ACS Catal. 207, 7: 584. [2] Zhang, F.; Chen, N.; Zhou, J.; Wu, R. ACS Catal. 206, 6: 698. [3] Zhou, J.; Wang, X.; Kuang, M.; Wang, L; Luo, H.; Mo, Y.;Wu, R. ACS Catal. 205, 5: 4466. 36

I-4-7 Two-Dimensional Materials for Electrocatalytic Water Splitting Chongyi Ling, Yixin Ouyang, Li Shi, Jinlan Wang* School of Physics, Southeast University, Nanjing 289 *Email: jlwang@seu.edu.cn Hydrogen produced through electrocatalytic water splitting has been regarded as one of the most promising candidates for the energy source of the next generation. Searching for efficient, stable and low cost catalysts for water splitting has thus become an urgent task. In this talk, I will discuss the design of electrocatalysts based on recently reported two-dimensional nanosheets like molybdenum disulfide (MoS2), MXenes and boron monolayer (BM), for water splitting. Our first-principle calculations demonstrated that formation of intrinsic defects including point defects and grain boundaries can activate the inert basal plane of MoS2 and greatly improve the hydrogen evolution reaction (HER) performance of MoS2. Template-grown MoS2 nanowires on Au(755) surface hold both ultra-low kinetic barriers for H2 evolution and ultra-high active site density simultaneously, which may achieve the greatest HER activity of MoS2 based catalysts. With the promotion of transition metals, vanadium carbides with fully oxygen terminated surface (V2CO2) can be tuned to be a highly active catalyst for HER. A simple activity descriptor (number of electron active site gains) is proposed to evaluate the HER performance through the molecular orbital theory. An effective screening among fully oxygen terminated mono-metal and bi-metal MXenes is performed based on this descriptor and Ti2CO2, W2CO2, TiVCO2 are extracted as promising catalyst for HER. β2, χ3, α and β boron monolayer (BMs) are found to possess high intrinsic HER activity without any decoration. The first single-atom bifunctional eletrocatalyst, single nickel atom supported on β2-bm is designed, to achieve overall water splitting. These findings provide new candidates for electrocatalysts for water splitting and offer cost-effective opportunities for advancing clean energy technology. Fig. Two-dimensional materials for water splitting. Keywords: two-dimensional layered materials; water splitting; electrocatalysis; hydrogen evolution reaction; oxygen evolution reaction References: [] Ouyang, Y.X.; Ling, C.Y.; Chen, Q.; Wang, Z.L.; Shi, L.; Wang, J.L. Chem. Mater., 206, 28: 4390. [2] Ling, C.Y.; Ouyang, Y.X.; Shi, L.; Yuan, S.J.; Chen, Q.; Wang, J.L. ACS Catal., 207, 7: 5097. [3] Ling, C.Y.; Shi, L.; Ouyang, Y.X.; Chen, Q.; Wang, J.L. Adv. Sci., 206, 3: 60080. [4] Ling, C.Y.; Shi, L.; Ouyang, Y.X.; Wang, J.L. Chem. Mater., 206, 28: 9026. [5] Shi, L.; Ling, C.Y.; Ouyang, Y.X.; Wang, J.L. Nanoscale, 207, 9: 533. [6] Ling, C.Y.; Shi, L.; Ouyang, Y.X.; Zeng, X.C.; Wang, J.L. Nano Lett., 207, 7: 533. 37

I-4-8 大规模反应分子动力学模拟新进展 李晓霞,2*, 郑默, 张婷婷,2, 韩嵩,2, 高明杰,2, 任春醒,2, 郭力,2 中国科学院过程工程研究所, 北京海淀区中关村北二街 号,0090 2 工作单位中国科学院大学化学化工学院, 北京,00049 *Email: xxia@ipe.ac.cn 由 van Duin 和 Goddard 等提出的反应力场 ReaxFF 与分子动力学 (Molecular dynamics, MD) 相结合, 能够描述分子体系化学反应随时间的演化, 且不需要预先假定反应路径, 因此在揭示复杂体系高温反应过程的反应机理方面应用前景诱人, 正在获得广泛应用 但 ReaxFF MD 依然计算强度大, 比经典 MD 模拟慢数十倍 ; 且对化学反应网络的分析具有挑战性 将作者课题组发展的国际领先的 GPU 并行程序系统 GMD-Reax 与化学反应自动分析程序系统 VARxMD 结合, 可使 ~0,000 原子规模甚至更大规模的反应分子动力学 (ReaxFF MD) 模拟应用在桌面机或单一计算节点上高效运行, 借助于升温模拟策略, 可考察近似于全景式产物随温度的演化规律及其蕴含的化学反应路径信息 利用先进的 GPU 卡如 NVIDIA Tesla K40 或 K80, 单 GPU 模拟的煤模型规模可达到 00,000 原子规模 - 0 万原子规模的无定形煤分子模型对于利用 ReaxFF MD 模拟揭示煤热解过程的反应机理极为重要, 特别是对于热解焦油的代表性产物如酚类 甲基萘等的生成与演化规律的观察, 0 万原子规模的煤模型必不可少 除了应用于煤热解机理研究外,GMD-Reax 与 VARxMD 的应用所揭示的生物质体系 ( 纤维素 木质素 ) 和碳氢燃料的热解过程的反应机理 以及生物油和碳氢燃料等的氧化反应机理也是实验方法及其他计算方法难以直接获得的 关键词 :ReaxFF MD; 热解与氧化 ; 反应机理 ; 大规模分子模拟参考文献 [] Han, S.; Li, X.; Nie F.; Zheng, M.; Liu, X.; Guo, L. Energy & Fuels 207 DOI: 0.02/acs.energyfuels.7b094 [2] Zheng, M.; Li, X.; Nie, F.; Guo, L. Energy & Fuels 207, 3: 3675 [3] Liu, X.; Li, X.; Nie, F.; Guo, L. Energy & Fuels 207, 3 (2): 608 [4] 王子民, 郑默, 谢勇冰, 李晓霞, 曾鸣, 曹宏斌, 郭力. 物理化学学报, 207, 33 (7):399 38

I-4-9 Theoretical Study on E-Ligand Cooperative Catalysis of Pincer-type Phosphorus Compound: A New Mode of Reaction Guixiang Zeng Kuang Yaming Honors School, University of Nanjing, Xianlin Road 63, Qixia Area, Nanjing, 20023 *Email: gxzeng@nju.edu.cn Main-group element compounds are promising cheaper and green alternatives to transition-metal complexes in catalysis for their excellent reactivities similar to those of transition-metal complexes in typical elementary reaction steps []. However, the catalytic cycles mediated by main-group element compounds are very rare as compared with those by transition-metal complexes. Therefore, constructing catalytic cycles are of crucial importance for the development of the catalysis of main-group element compounds, which would provide new possibilities for chemical syntheses. Radosevich et al. reported a transfer hydrogenation reaction of azobenzene with NH3BH3 by a phosphorus compound P in 202 [2]. We theoretically investigated this reaction with DFT, CCSD(T) and ONIOM (CCSD(T):MP2) methods, where GRRM program was employed to search for transition states [3]. Our computational results demonstrate that the reaction occurs through a phosphorus-ligand cooperation catalytic cycle as shown in Scheme, in which the phosphorus oxidation state changes between +I and +III. This electronic feature is different from that of the metal-ligand cooperation catalytic cycle, where the metal oxidation state does not change. We also explored the substituent and framework effects on the activity of P. More effective pincer-type phosphorus compound was theoretically designed, which has wider applications than the experimentally reported one [4]. Scheme. Reaction mechanism of the transfer hydrogenation reaction mediated by P. Keywords: Phosphorus, Cooperative Catalysis, Transfer Hydrogenation, DFT References: [] Power, P. P. Nature 200, 463: 7. [2] Dunn, N. L.; Ha, M.; Radosevich, A. T. J. Am. Chem. Soc. 202, 34: 330. [3] Zeng, G.; Maeda, S.; Taketsugu, T.; Sakaki, S. Angew. Chem. Int. Ed. 204, 53: 4633. [4] Zeng, G.; Maeda, S.; Taketsugu, T.; Sakaki, S. Acs Catal. 206, 6: 4859. 39

I-4-20 聚苯乙烯粗粒化模型的构建 : 结构 热力学 动力学 肖强, 郭洪霞,* 中国科学院化学研究所, 北京市海淀区中关村北一街 2 号, 0090 *Email: hxguo@iccas.ac.cn 众所周知, 实现对高分子材料的性能优化和新功能开发的关键是深入认识结构和动力学 当前, 模拟计算已发展成为独特的高分子科学研究手段 通常对高分子材料结构与动力学的模拟研究会涉及比较大的时空尺度, 传统的原子水平的模拟方法不能满足实际应用研究的需求 而近些年提出的系统粗粒化方法, 因其在大幅提高计算效率的同时还能一定程度保留体系特有的细节性质, 获得了广泛关注 然而, 粗粒化模型的可靠运用强烈依赖于模型的迁移性 ( 对体系参数化目标性质在不同热力学条件下的重复性 ) 和代表性 ( 对体系的非参数化目标性质的重复性 ), 目前如何实现这两个要求在模拟研究领域仍然是重大挑战 无规聚苯乙烯 (PS) 体系是一类具有广泛用途的热塑性塑料, 但现有的粗粒化方法所得到的 CG 模型, 不能同时满足简单高效建模及良好的温度迁移性和代表性 ( 以至于能用于实际玻璃态体系的结构和动力学研究 ) 两个实际应用的要求 因此, 我们以 PS 作为研究体系, 从两个层面开展工作 : 一是从方法学层面, 探索如何从力场的非键势和成键势两个角度优化现有的结构基 - 热力学基联合粗粒化方法, 以进一步提高 CG 模型的温度迁移性, 使其能够运用于研究 PS 玻璃态体系的相关性质 ; 二是从应用层面, 利用我们优化的 CG 模型, 对无规 PS 体系展开具有代表性的应用研究, 如考察 CG 模型在重现体系玻璃化转变温度 Tg 特征结构和玻璃化转变动力学方面的潜力 关键词 : 系统粗粒化 ; 聚合物结构 ; 热力学性质 ; 玻璃化转变温度 ; 玻璃化转变动力学参考文献 [] Qiang Xiao and Hongxia Guo*, Phys.Chem.Chem.Phys., 206, 8(43):29808-29824 40

I-4-2 在线计算化学 I: 分子静电计算与可视化 卢本卓 *, 白石阳, 刘田田, 陈旻昕, 乔瑜, 彭波 科学院计算数学与科学工程计算研究所, 北京 0090 *Email:bzlu@lsec.cc.ac.cn 摘要 : 本报告介绍基于在线计算网站 xyzgate.com 的计算化学研究, 主要以生物分子的 PB 静电计算模拟作为例子 在线计算具有多方面的优点, 如方便自由地开辟和关闭计算节点, 计算 分析 存储 使用等一体化在线完成 这将为计算研究工作者提供新的工作方式 这里将介绍和展示在线使用我们自己开发的部分计算软件及算例, 包括 : 最新发展的高效分子表面三角化的 TMSmesh2 软件, 可对大分子表面快速三角化, 进行分子几何特征及求解 PB 方程等的计算 ; 大规模并行自适应快速多极子 Poisson-Boltzmann 静电计算程序 pafmpb, 可对较大的分子快速计算溶剂化能自由能计算 ; 同时对生物分子结构 分子表面和电势分布算例的部分结果进行在线可视化分析 Fig. Online computing/visualization on xyzgate.com 关键词 : 在线计算,Poisson-Boltzmann 静电, 分子表面, 可视化 参考文献 :. xyzgate.com. 2. Tiantian Liu, M.X. Chen, and B.Z. Lu, Efficient and qualified mesh generation for Gaussian molecular surface using adaptive partition and piecewise polynomial approximation, https://arxiv.org/pdf/6.03474.pdf,206 (submitted to SIAM J. Sci. Computing) 3. Minxin Chen, Benzhuo Lu, TMSmesh: A robust method for molecular surface mesh generation using a trace technique, J. Chem. Theory Comput., 7:203-22, 20 4. Shiyang Bai, Benzhuo Lu, VCMM: A visual tool for continuum molecular modeling, J. Molecular Graphics and Modelling, 50: 44-49, 204. 5. Bo Zhang, Bo Peng, Jingfang Huang, Nikos P. Pitsianis, Xiaobai Sun, Benzhuo Lu, Parallel AFMPB solver with automatic surface meshing for calculations of molecular solvation free energy, Computer Physics Communications, 90: 73 8, 205. 4

I-4-22 Ras 蛋白超粗粒化模型的发展 夏飞 *,,, 曹泽星, 张增辉, 化学与分子工程学院, 华东师范大学, 邮编 200062 厦门大学化学化工学院, 厦门大学, 邮编 36005 上海纽约大学 - 华师大联合计算中心, 上海纽约大学, 邮编 200062 *Email: fxia@chem.ecnu.edu.cn 摘要 : 粗粒化模型被广泛地应用于蛋白质结构与功能的研究, 发展蛋白质的粗粒化模型为生物大体系的多尺度模拟提供了重要的理论工具 近期, 我们尝试了发展了蛋白质超粗粒化模型, 超粗粒化模型跟目前国际上的粗粒化模型相比具有更低的分辨率 我们已经发展了针对蛋白质体系超粗粒化的快速优化方法 (FM-CG) 与算法 (SLIO), 利用这些方法可以优化得到蛋白质体系的超粗粒化表达 我们进一步利用经验的势能函数对超粗粒化粒子进行了参数化, 并构建了蛋白质有效的超粗粒化模型 我们将运用发展的超粗粒化模型来模拟研究蛋白质复合物的动力学性质与功能 Figure (a) Crystal structure of Ras. (b) Ultra coarse-grained model of Ras and PCA. 关键词 : 超粗粒化模型 ; Ras 蛋白 ; 多尺度模拟参考文献 [] Zhang, Y. W.; Cao, Z. X.; Xia, F.* Chem. Phys. Lett. 207, 68,. [2] Zhang, Y. W.; Cao, Z. X.; Zhang, J. Z. H.; Xia, F.* J. Chem. Inf. Model.207, 57, 24. [3] Li, M.; Zhang, J. Z. H.; Xia, F.* J. Chem. Theory Comput. 206, 2, 209. [4] Li, M.; Zhang, J. Z. H.; Xia, F.* J. Comput. Chem. 206, 37, 795. 42

I-4-23 Dynamics of carbon monoxide dissociation on Co( 0) Xixi Hu *, Bin Jiang 2, Hua Guo 3, Daiqian Xie * Institute of Theoretical and Computational Chemistry, Key Laboratory of Mesoscopic Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 20093 2 Department of Chemical Physics, University of Science and Technology of China, Hefei 230026 3 Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 873, USA Dissociative chemisorption (DC) is the initial and often rate-limiting step in heterogeneous catalysis. Many such processes are direct and as a result the dissociation is largely controlled by the dissociation transition state. Static DFT calculations of the barrier properties provide reasonably accurate estimates of the reactivity in most such cases. Simple transition-state based models such as SVP have also been quite successful in predicting mode specificity in DC processes. However, the picture is no longer so simple for indirect dissociation processes such as the case discussed here. To gain insights into such a prototypical interfacial process, we report the first six-dimensional PES for carbon monoxide DC on a Co surface. The topography of the PES is quite complex and stable adsorption configurations and transition state found on the PES are in good agreement with the available experimental and theoretical results. Using this PES, QCT calculations were performed for studying the dynamics of CO DC on Co( 0), shedding light on the dynamics of this important reaction. The barrierless pathway leading to the chemisorption well allows the impinging molecule to form a precursor state, in which the adsorbed molecule stay for a significant (ps) residence time. Despite a low barrier, it is found that the dissociation is very inefficient, due to difficulties in energy flow into the dissociation reaction coordinate. Only those trajectories with the CO near the hollow site parallel to the surface with an elongated C-O bond dissociate. However, the dissociation can be promoted by increasing the incident energy, although not significantly affected by changing the incident angle. In addition, vibrational and rotational energy are more effective than the same amount of translational energy for the enhancement of reactivity. The apparent mode specificity suggests the energy is not entirely randomized in the chemisorption well and the memory of the initial excitation in the impinging molecule survives. The apparent low reactivity over a small reaction barrier in this process raises an important question concerning the conventional way of characterizing surface processes solely based on DFT barrier heights. For this initial step in the FTS, the low barrier for dissociation does not lead to high dissociation probability, underscoring the importance of dynamics. Our work here thus offers a caveat to kinetic modeling of catalytic processes in general. More dynamical studies are clearly needed to elucidate the catalytic mechanism and kinetics of the FTS. 43

I-4-24 First-principles Evaluation of Catalytic Performance of Zeolite Zhai Dong ( 翟冬 )and Liu Yi, * ( 刘轶 ) Department of Physics, Materials Genome Institute (MGI), and International Centre for Quantum and Molecular Structures (ICQMS) Shanghai University, 99 Shangda Road, Shanghai 200444, P. R. China *Email: yiliu@shu.edu.cn Catalytic reactions of zeolites mainly occurring at their acid sites are associated with both the host structures and the origins of acid site formation; however, there is a lack of comprehensive quantitative method to characterize the acid sites from both thermodynamic and kinetic aspects. Here we propose a comprehensive computational approach to evaluate jointly the energetic stability, space accessibility, and acid strength (SAS) critical to the catalytic performance of acid sites in zeolites. In this approach, we evaluated the SAS systematically for various potential Brønsted acid sites in zeolites, using density functional calculations. The total energy was used to compare the relative stabilities of various acid sites of the same type. The deprotonation energy (DPE) was calculated to represent the acid strength. Moreover, we proposed a concept of local accessible surface area (LASA) to measure the accessibility of a localized surface region of molecular sites of complex shape. The SAS were evaluated comprehensively for various Brønsted acid sites including bridging hydroxyl (BH), nest hydroxyl (NH) and terminal silanol (TS) in the internal pores and on the external surfaces of MFI-type zeolite. We found the acid sites in descending order of stability to be the Al2/H2, Al9/H2, and Al/H sites of intra-crystalline BH, and BH on the (00) and (00) external surfaces. The most stable NH sites in descending order were located at the T4, T7 and T5 defective sites in the internal pores, and on the (00) and (00) external surfaces. The accessibility of an acid site depends on the OH orientation at the studied acid site. Most of the NH sites are difficult to access due to the connected hydrogen bonds. The acid strength of the studied Brønsted acid sites decreases as BH > NH> TS. Both the pore geometry and hydrogen bonds can enhance the acid strength. The first-principles computational evaluation of the SAS to characterize acid sites provides a comprehensive approach that facilitates evaluation of catalytic performance for the design of zeolite catalysts. [] Keywords: Zeolite; Acid strength; Density functional calculations; Surface area; Deprotonation energy References: [] Zhai, Dong; Liu, Yi et. al. Journal of Catalysis 207, 352: 627 637 44

I-4-25 Hydrolysis of Atmospheric Molecules and Ion-induced Nucleation of Aerosols Clusters Shixian Wang, Zheng Zhao, Hui Li* hli@buct.edu.cn Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology The hydrolysis of SO2 is a traditional source of gaseous sulfuric acid in the atmosphere. To account for the effect of temperature and catalysts on the hydrolysis reaction of SO2, we carried on Ab initio molecular dynamics (AIMD) simulation investigations on SO2+nH2O (n=, 2)+acid (H2SO4, H2SO3, HNO3). Temperature, combined with the number of water molecules and assistant acid molecules, have a great influence on the reaction free energy. These three kinds of acids all have excellent catalytic ability. We reveal the entropic effects plays important role on the dynamics of the motion of the reaction, which can make atmospheric chemical reaction become thermostatically favorable at higher temperature. Aerosol particles in the atmosphere are important participants in the formation of haze pollution and have significant impact on cloud albedo and global climate. In this study, we combined ab initio molecular dynamics simulations (AIMD) with classical nucleation theory (CNT) to study ion-induced nucleation of aerosols clusters including pure H2O, H2O-H2SO4, H2O-NH4HSO4, and H2O-NH3 at the size of -3nm. The normal component pressure tensor P_N (r) and surface tension σ of aerosols clusters are calculated and which show good consistence with the results from previous simulations. The Gibbs free energy change of aerosol clusters showed that small aerosol clusters nucleation can also become spontaneous without crossing the nucleation barrier, because the SO4 2- and NH4 + ionized from NH4HSO4 and H2SO4 have a stronger interaction with H2O, which firstly gives a reasonable explanation for experiment phenomenon from a theoretical point of view. Moreover, the strength order of promoting effect on the nucleation of aerosol clusters is NH4HSO4> H2SO4> NH3 in spite of the weak effect of NH3. 45

I-4-26 Investigation molecular dissolution mechanism of ketoprofen ternary solid dispersions by molecular dynamics simulations Weijie Chen, Defang Ouyang,* State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS), University of Macau, Macau, China *Email: defangouyang@umac.mo [Introduction] Ketoprofen (KET) is a poorly-water soluble drug. To improve the solubility and dissolution rate of ketoprofen, previous experiments developed KET - Polyethylene Glycol (PEG) - Tween 60 (TWE) and KET - PEG - Sodium Dodecyl Sulfate (SDS) ternary solid dispersion. In the ternary solid dispersion system, the addition of a nonionic surfactant TWE or an anionic surfactant SDS could effectively improve the solubility and dissolution rate of KET. However, the mechanism of dissolution improvement is still unclear. Thus, the research aimed to investigate the molecular dissolution mechanism of different surfactants in ternary solid dispersions by molecular dynamics simulations. [Methods] AMBER4 software was used for molecular dynamics simulations. The general AMBER force fields (gaff and ff4sb) were applied for drugs, carriers and surfactants. All molecules were built by the Discovery Studio Visualizer 3.. Simulations annealing method was intended to mimic hot melting method in the experiments. Then the model system was immersed in a wrapping water box with a solvation shell of 30 Å thickness using TIP3P model for water. [Results] The simulated annealing method was performed to simulate the preparation of solid dispersions, and the dissolution processes were simulated by molecular dynamics. The simulation results indicated that drug molecules in ternary system with SDS was easier to be released into the water than that with TWE, as shown in Figure. These modeling results were in well agreement with the experimental results. For the ternary solid dispersions, the additional surfactant can improve the wettability of the drug molecules and the structure of the random coils, which can help the drug molecules to escape from the system easily. [Conclusions] This research presented reasonable explanation to dissolution molecular mechanism of ternary solid dispersions. Our research will also benefit pharmaceutical scientists to develop the formulations of ternary solid dispersions. Figure. (a) The initial structure of KET-PEG-SDS with solvent; (b) final structure after dissolution without solvent. Keywords: Ketoprofen, Surfactans, Solid Dispersion, Molecular dynamics, Dissolution molecular mechanism References: [] Weijie Chen & Defang Ouyang, Molecular Simulation, 207, DOI: 0.080/08927022.207.32755 46

I-4-27 分支酸酶家族产品调控机制的研究 张玉来, 郑清川,* 吉林大学理论化学研究所, 吉林长春, 邮编 :30023 *Email: zhengqc@jlu.edu.cn 分支酸代谢相关途径是抗菌药物和除草剂研发的重要靶标 最近, 一类新的分支酸代谢酶被定义 [-2] 分支酸酶家族 该家族除可被用作药物研发靶点外, 其代谢物还可应用于多种临床药物的合成 分支酸酶家族包括三个子类 :FkbO [3],Hyg5 [4],XanB2 [5], 三者催化相同的底物 分支酸, 却存在不同的产品选择性 FkbO 催化分支酸生成 3,4-trans-CHD;Hyg5 催化分支酸生成 3-HBA; 而 XanB2 催化分支酸生成 3-HBA 和 4-HBA 的混合产品 同位素追踪实验证实分支酸酶家族的产品选择性来源于三者催化反应机理的差异,FkbO 催化机制属于典型的水解机制, 即反应过程需要水的参与 ; 而 Hyg5 和 XanB2 催化机制属于分子内机制, 反应过程不需要水的参与 换言之,3,4-trans-CHD 是通过水解机制得到的, 而 3-HBA 和 4-HBA 则是分子内机制的产物 因此, 其产品调控机制可被描述为 : 单一保守位点下, 一种底物 - 两种催化机制 - 三种产物的关系 现今的研究工作多认为活性中心附近 A/G 残基组是主要的调控因素 但基于实验和计算的结果, 通过考察之前研究工作中忽视的重要因素 水分子的运动特征, 我们找到了一组诱导差异的残基组 V/Q V/Q 互相突变, 水分子特性且其催化机制也随之交换,V/Q 或许才是影响分支酸酶家族产品调控的关键因素 该研究成果将会为分支酸酶家族产品调控机制的研究带来新的观点和解释 Fig. the distribution of water at active site for FkbO, V209Q-FkbO, Hyg5 and Q20V-Hyg5 关键词 : 分支酸酶 ; 产品调控机制 ; 水通道参考文献 [] Shoda S, Uyama H, Kadokawa J, Kimura S, Kobayashi S, Chem Rev, 206, 6: 2307-243. [2] Maeda H, Dudareva N, Annu Rev Plant Biol, 202, 63: 73-05. [3] Hubrich F, Juneja P, Muller M, Diederichs K, Welte W, et al. J Am Chem Soc, 205, 37: 032-037. [4] Andexer JN, Kendrew SG, Nur-e-Alam M, Lazos O, Foster TA, et al. Proceedings of the National Academy of Sciences, 20,08: 4776-478. [5] Zhou L, Wang JY, Wu J, Wang J, Poplawsky A, et al. Mol Microbiol, 203, 87: 80-93. 47

O--0 PDB 数据库中被低估的卤键徐志建中国科学院上海药物研究所, 上海市浦东新区祖冲之路 555 号,20203 *Email: zjxu@simm.ac.cn 统计表明, 约三分之一可供虚拟筛选的有机化合物 四分之一的上市药物含有卤素 近年来, 卤素与药物靶标之间形成的卤键作用已在药物设计领域引起广泛关注 现有的晶体结构精修方法和软件未考虑卤键作用, 可能会导致蛋白质晶体结构数据库 (PDB) 中本应真实存在的卤键减弱 甚至消失 通过比较不同分辨率下侧链卤键占总卤键的百分比, 我们证实了侧链卤键在 PDB 数据库中被低估 ; 通过比较不同分辨率下主链卤键的 RF 值 ( 实际出现的频率 / 随机情况下出现的频率 ), 我们证实了主链卤键在 PDB 数据库中亦被低估 因此, 有必要对 PDB 结构进行重新精修, 以恢复真实存在的卤键信息 关键词 : 卤键 ;PDB; 晶体结构 Fig. Halogen bonds are overlooked in protein data bank. 参考文献 [] Zhang, Q.; Xu, Z.; Zhu, W., The Underestimated Halogen Bonds Forming with Protein Side Chains in Drug Discovery and Design. J. Chem. Inf. Model. 207, 57: 22. [2] Zhang, Q.; Xu, Z.; Shi, J.; Zhu, W., Underestimated Halogen Bonds Forming with Protein Backbone in Protein Data Bank. J. Chem. Inf. Model. 207. DOI: 0.02/acs.jcim.7b00235. 48

O--02 2D/3D-QSAR 方法相结合筛选与发现具有新型骨架结构的 CDPK 抑制剂李书艳 *, 张鹏翼, 郏丽佩 兰州大学, 甘肃省兰州市兰州大学化学化工学院,730000 *Email: lishuyan@lzu.edu.cn 基于配体的药物设计往往局限于已有的模版骨架, 无法回避其固有的药代动力学相关问题 手动设计全新结构的方法需要设计人员具有海量的背景知识并存在低可靠性等问题 为此, 在本工作中我们以 CDPK 抑制剂为例, 开发一种基于 2D/3D-QSAR 建模 骨架跃迁方法与组合库设计相结合的方法, 可以在已有抑制剂结构的基础上, 设计出具有全新骨架的抑制剂并将其活性进行生化验证 该方法可为解决活性化合物的骨架结构更新提供一条自动化的新路 图. 具有较高活性的 CDPK 抑制剂的全新骨架结构 关键词 :2D-QSAR, 3D-QSAR, 骨架跃迁, 组合库设计 参考文献 [] Lourido, S., et al., Nature, 200, 465: 359-362. [2] Andricopulo, A.D., Curr. Top. Med. Chem, 2009, 9: 754 [3]Gharwan, H. and H. Groninger, Nat. Rev. Clin. Oncol., 206, 3: 209-227. 49

O--03 计算机辅助多靶点抗抑郁药物作用机制研究 *,2* 薛伟伟, 王盼盼, 郑国勋, 杨凤园, 朱峰 重庆大学药学院, 重庆市沙坪坝区大学城南路 55 号,4033 2 浙江大学药学院, 浙江省杭州市西湖区余杭塘路 866 号,30058 *Email: xueww@cqu.edu.cn( 薛伟伟 ),zhufeng.ns@gmail.com( 朱峰 ) 多靶点药物在复杂疾病 ( 如癌症 糖尿病和中枢神经系统疾病等 ) 治疗中具有疗效好和副作用低的优势 近年来, 计算机辅助多靶点药物设计也越来越多的受到关注 抑郁症是一种常见的精神疾患 突触间隙神经递质如 5- 羟色胺 (5-HT) 去甲肾上腺素 (NE) 和多巴胺 (DA) 浓度的降低是导致其发生的重要原因 目前, 虽然已经基于 5- 羟色胺转运体 (SERT) 和去甲肾上腺素转运体 (NET) 发出了单靶点抗抑郁药物 ( 如 SSRI 和 snri), 遗憾的是它们起效相对缓慢且具有明显的副作用 因此, 针对与 5-HT NE 和 DA 再吸收相关的 SERT NET 和 DAT 设计多靶点抑制剂将是新型抗抑郁药物研发的一个热点和重要方向 本工作运用同源模建 分子对接 分子动力学模拟和结合自由能计算的组合计算方法, 系统研究了应用广泛的单靶点抗抑郁药物 SSRI 和 snri 双靶点药物 SNRIs 和正在临床研究中的三靶点药物 TRI 分别与靶点 SERT NET 和 DAT 的相互作用模式 识别了 SSRI snri SNRI 和 TRI 在结合不同靶点的过程中起到关键作用的共同氨基酸 通过比较发现这些抗抑郁剂有着类似的作用机制 : 小分子中含质子化氮的基团与 Asp98 (SERT) 或 Asp75(NET) 或 Asp79(DAT) 形成静电相互作用 ( 盐桥和氢键 ), 起药物和靶点识别的作用 ; 另外两个脂溶性基团在相应的疏水性口袋与对应氨基酸发生疏水性相互作用, 起区分单靶和多靶选择性的作用 本研究为多靶点抗抑郁药物的设计提供了坚实的结构和能量基础, 同时也将为其他多靶点药物作用机制的研究和多靶点药物设计提供了思路 Fig. Schematic diagram of the inhibitory mechanism of dual target antidepressant SNRI with SERT/NET. 关键词 : 多靶点药物 ; 单胺转运蛋白 ; 同源模建 ; 分子动力学模拟 ; 自由能计算 参考文献 [] Penmatsa, A.; Wang, K.H.; Gouaux, E. * Nature 203, 503: 85. [2] Anighoro, A.; Bajorath, J.; Rastelli, G. * J. Med. Chem. 204, 57: 7874. [3] Xue, W.; Wang, P.; Li, B.; Li, Y.; Xu, X.; Yang, F.; Yao, X.; Chen, Y.Z.; Xu, F.; Zhu, F. * Phys. Chem. Chem. Phys. 206, 8: 3260. [4] Zheng, G.; Xue, W. * ; Wang, P.; Yang, F.; Li, B.; Li, X.; Li, Y.; Yao, X.; Zhu, F. * Sci. Rep. 206, 6: 26883. [5] Wang, P.; Zhang, X.; Fu, T.; Li, S.; Li, B.; Xue, W. * ; Yao, X.; Chen, Y.; Zhu, F. * ACS Chem. Neurosci. 207, 8: 46. 感谢国家自然科学基金青年科学基金项目 (No. 2505009, 8202459) 的资助 50

O--04 A simple approach to enhance the temperature transferability of all-atom force field Zheng Gong, Huai Sun * School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240 *Email: huaisun@sjtu.edu.cn It is desirable to predict the thermodynamic and transport properties of materials and industrial liquids from molecular simulation, which is less expensive than experimental measurements, especially at extreme conditions such as high temperature and high pressure. The successful prediction of the properties and behaviors of materials relies on the accuracy of force field. Most of the classical all-atom force fields like OPLS/AA[], COMPASS[2], CGenFF[3] and our recently developed TEAMFF[4] are optimized for ambient temperature. For biological simulations, there is no problem. However, when it comes to material simulation, the temperature transferability becomes important because many chemical engineering processes happens at elevated temperature. In this work, a simple approach to enhance the temperature transferability of all-atom force field is proposed. Considering the temperature dependence of polarizability of molecules, we write the van de Walls parameters linearly dependent on temperature. The optimization was performed for 32 alkane molecules at different temperatures simultaneously. Compared with TEAMFF, this new force field gives more accurate density and enthalpy of vaporization at large temperature range from 00 to 500 K. Fig. The experimental and simulated density and enthalpy of vaporization of ethane, propane, hexane and dodecane at different temperatures. Keywords: all-atom force field; temperature transferability References: [] Jorgensen, W. L.; Jorgensen, W. L.; Maxwell, D. S.; Maxwell, D. S.; Tirado-Rives, J.; Tirado-Rives, J. J. Am. Chem. Soc. 996, 8 (5), 225 236. [2] Sun, H. J. Phys. Chem. B 998, 02 (38), 7338 7364. [3] Vanommeslaeghe, K.; Hatcher, E.; Acharya, C.; Kundu, S.; Zhong, S.; Shim, J.; Darian, E.; Guvench, O.; Lopes, P.; Vorobyov, I.; Mackerell, A. D. J. Comput. Chem. 200, 3 (4), 67 690. [4] Jin, Z.; Yang, C.; Cao, F.; Li, F.; Jing, Z.; Chen, L.; Shen, Z.; Xin, L.; Tong, S.; Sun, H. J. Comput. Chem. 206, 37 (7), 653 664. 5

O--05 基于系统药理学的药物副作用预测与药物作用机制研究 曹东升, 陈丰原 2 中南大学湘雅药学院, 长沙市岳麓区桐梓坡路 72 号,40003 2 中南大学湘雅三医院, 长沙市岳麓区桐梓坡路 7 号,40003 *Email: oriental-cds@63.com 系统药理学在药物研究过程中已取得了广泛的应用和关注 本文重点讨论了基于系统药理学思想进行药物副作用预测和药物作用机制研究的案例 通过整合多尺度多水平药物信息进行了药物副作用的预测, 获得了满意的预测模型, 并能够指导临床药学人员进行药物副作用的监测和评估 运用系统药理学思想整合了多个尺度的药物和靶标的信息, 并基于推荐系统构建了药物 - 靶标预测模型 该模型预测了多个药物的新作用机制 其中发现伊沙匹隆结合抗凋亡蛋白 BCL-2, 并进行了实验验证, 深入研究发现了伊沙匹隆通过 BCL-2 产生自噬耐药性的新机制, 即伊沙匹隆在乳腺癌细胞中能够通过抑制抗凋亡蛋白 BCL-2 诱导自噬发生, 而自噬对伊沙匹隆诱导的乳腺癌细胞凋亡起到保护作用, 从而使得伊沙匹隆对乳腺癌治疗产生了耐药性 关键词 : 系统药理学 ; 药物副作用 ; 药物作用机制 ; 自噬耐药 ; 自噬抑制剂 参考文献 [] Cao D S., Nan Xiao,et al. Integrating multiple evidence sources to predict adverse drug reactions based on a systems pharmacology model. CPT: pharmacometrics & systems pharmacology, 205,4(9), 498-506. [2] Yao Zhi-Jiang, Cao D-S., et al. TargetNet: a web service for predicting potential drug target interaction profiling via multi-target SAR models. Journal of computer-aided molecular design, 206,30(5), 43-424. 52

O--06 Knowledge-based Pose Filter Ensemble as Structure-based Virtual Screening Tools to Facilitate the Discovery of FXR Agonists Jie Xia, #, Yi Huan, #, Xing Wang, Wenjie Xue, Xiang Simon Wang 2, Zhufang Shen, *, Song Wu,* State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 00050, China; 2 Molecular Modeling and Drug Discovery Core Laboratory for District of Columbia Center for AIDS Research (DC CFAR), Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20059, U.S.A. *Email: S.W. (ws@imm.ac.cn) or Z-F.S (shenzhf@imm.ac.cn) Structure-based virtual screening (SBVS) has become an indispensable technique for hit identification at the early stage of drug discovery. However, the accuracy of current scoring functions is not high enough to confer success to every target and thus remains to be improved. Previously, we developed binary pose filters (PFs) using knowledge derived from the protein-ligand interface of a single X-ray structure of a specific target and it had been validated as an effective way to improve ligand enrichment. Most recently, we developed PF ensembles (PFEs) that incorporate knowledge collected from diverse protein ligand interfaces of multiple crystal structures of the same target. We have validated its efficacy in boosting ligand enrichment by theoretical calculations and explored its advantages over the single PFs. Most importantly, we have found that it is the higher chemical diversity of protein-ligand interfaces that leads to the improved performance of PFEs. Farnesoid X receptor (FXR) is a potential target for the treatment of nonalcoholic fatty liver disease (NAFLD). Though many FXR agonists are currently available, none of them has been approved by FDA to treat NAFLD so far. It is always necessary to discover chemically dissimilar series of FXR agonists in case the known ones fail to enter the next stage of drug R&D pipeline due to unknown shortcomings. As for this target, we noticed that multiple crystal structures of FXR bound to its agonists were available in Protein Data Bank (PDB) and the benchmarks for FXR agonists from NRLiSt BDB were ready-to-use. It prompted us to construct PFE for this target and applied it to SBVS protocols. The benchmarking study showed that the PFE-coupled Chemgauss4 performs better than Chemgauss4 alone. Further large-scale VS facilitated by PFE identified a novel-scaffold FXR agonist from the Specs chemical library. Moreover, we tested its pharmacological effect on the nonalcoholic fatty liver disease (NAFLD) in vitro. The result has shown promising outcome on the cell model of oleic acid-induced hepatic steatosis. Currently, we are working on more experiments to validate its effects. Keywords: pose filter; structure-based virtual screening; Farnesoid-X receptor; novel scaffold References: [] Zhang, S.; Golbraikh, A.; Tropsha, A. J. Med. Chem. 2006, 49: 273. [2] Hsieh, J.H., Yin, S., Wang, X.S., Liu, S., Dokholyan, N.V., Tropsha, A. J. Chem. Inf. Model. 202, 52:6. [3] Fourches, D.; Politi, R.; Tropsha, A. J. Chem. Inf. Model. 205, 55: 63. [4] Politi, R.; Convertino, M.; Popov, K.; Dokholyan, N. V.;Tropsha, A. J. Chem. Inf. Model. 206, 56: 032. [5] Xia, J.; Hsieh, J.H.; Hu, H.; Wu, S.; Wang, X.S. J. Chem. Inf. Model. 207, 57:44. 53

O--07 基于药效片段组合的新型蛋白激酶 CK2 抑制剂设计 * 周玥, 齐晓倩, 唐珊, 张娜 北京工业大学生命科学与生物工程学院, 北京市朝阳区平乐园 00 号,00020 *Email:nanatonglei@bjut.edu.cn 蛋白激酶 CK2 作为一类重要的多功能蛋白激酶, 具有促增长且抗凋亡的特性而成为重要的抗癌靶标 [], 以其为靶点的抗癌药物研发具有重要的临床价值及良好的应用前景 基于已有 CK2 与其抑制剂复合物的晶体 结构, 并根据抑制剂与活性口袋极性作用方式的不同, 可将抑制剂分为三类 ( 图 ): 第 I 类仅与铰链区形成 极性作用, 如 TBB 及 DAA; 第 II 类仅与正电区形成极性作用, 如 Emodin 及 DBC 第 III 类是可同时与铰链区 和正电区形成极性作用, 如化合物 CX-4945, 具有较高的抑制活性 兼顾化合物骨架类别及药效基团的完整 性原则, 运用 Lephar 软件包 [2], 对已有 CK2 小分子抑制剂进行拆分和对接, 得到 363 个关键药效基团片段, 其中芳香性环状结构约占 90%, 且多数为含有氨基 羟基或者羰基等氢键供体或者受体 如图 2 所示, 代表 性关键药效基团片段包括 : 与铰链区形成氢键的氨基 羟基及吡啶环等杂环, 以及与正电性区 Lys68 形成极 性作用的羟基及羧基等负电性基团 该虚拟药效基团数据库的构建, 可为基于片段组合策略的 CK2 抑制剂设 计提供结构素材来源 Figure Three types of CK2 inhibitors binding mode Figure 2 The pharmacophore fragments of CK2 inhibitors 关键词 : 蛋白激酶 CK2; 抑制剂 ; 药效片段 ; 药物设计 参考文献 [] Cozza, G.; Pinna, LA. Expert. Opin. Ther. Targets. 206, 20(3): 39. [2]Zhao, H.; Caflisch A. Bioorg. Med. Chem. Lett. 205, 25():2372. 54

O--08 Predicting binding affinity of compound-protein interactions on a proteome scale by random forest using network topology features Zhanchao Li,3 *, Yang Wang 2, Wenqian Zhong 2, Yun Xie, Zong Dai 2, XiaoYong Zou 2* School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Guangzhou, 50006 2 School of Chemistry, Sun Yat-Sen University, Guangzhou, 50275 2 Key Laboratory of Digital Quality Evaluation of Chinese Materia Medica of State Administration of Traditional Chinese Medicine, Guangzhou, 50006 *Email: zhanchao8052@gdpu.edu.cn; ceszxy@mail.sysu.edu.cn Identification of interactions between compounds and target proteins is of extraordinary significance to modern pharmacology and drug discovery []. Despite the advances in experiment technology, the determination of compound-target protein interactions at proteome scale is still expensive, laborious and time consuming. Therefore, various computational models have been developed to predict compound-protein interactions. The existing methods only infer whether a compound interacts with a target protein. In fact, binding affinity between a compound and a target protein is a more informative measure that reflects how tightly a compound binds to a specific protein. In this study, a comprehensive network is firstly constructed, including compound similarity subnetwork, protein interaction subnetwork and compound-protein interaction subnetwork. Each node in the network is weighted with molecular fingerprint descriptors or protein primary sequence features, each edge is weighted by compound similarity score, protein interaction confidence score or interaction affinity of compound-protein. Secondly, network topology features are proposed based on the graph theory. Thirdly, random forest is utilized to construct mode for predicting binding affinity of compound-protein interaction. Based on the 0-fold cross-validation test, the Spearman and Pearson correlation coefficient of 0.8547 and 0.8779 as well as root mean square error of 0.8638 are obtained, indicating the effectiveness of the developed method. Through randomly combining compounds from the subnetwork of compound similarity with proteins from subnetwork of protein-protein interaction, about 300,000 compound-protein interaction pairs are generated and their binding affinity are predicted. The results reveal that 202 predicted compound-protein interaction pairs with 404 compounds and 7 proteins have the values of Ki lower than 0 um. Based on the UniprotKB [2] and BrugBank [3] database, the 7 proteins and 404 compounds are further analyzed, in which 23 and 52 proteins are associated with disease and targets, and of the 404 compounds, 244, 33, 9, 67 and 20 drugs are the approved, experimental, illicit, investigational and withdrawn. Keywords: Binding affinity; Network; Graph theory; Random forest; Fingerprint References: [] Yuan, Q.; Gao, J.; Wu, D.; Zhang, S.; Mamitsuka, H.; Zhu, S. Bioinformatics 206, 32: i8-i27. [2] Boutet, E.; Lieberherr, D.; Tognolli, M., Schneider, M.; Bairoch, A. Methods Mol. Biol. 2007, 406: 89-2. [3] Law, V.; Knox, C.; Djoumbou, Y.; Jewison, T.; Guo, A.; Liu, Y.; Maciejewski, A.; Arndt, D.; Wilson, M., Neveu, V.; Tang, A.; Gabriel, G.; Ly, C.; Adamjee, S.; Dame, Z.; Han, B.; Zhou, Y.; Wishart, D. Nucleic Acids Res. 204, 42: D09-D097. *This work was funded by the National Natural Science Foundation of China (2675035, 267580, 2606053) 55

O--09 P(BDTn-DTBT) 和 P(BDTn-fDTBT) 分子与材料性质 的理论计算李佳, 李唯实, 李靖靖 2,2,*, 姚建华 中国科学院上海有机化学研究所, 上海市零陵路 345 号,200032 2 郑州工程技术学院, 化工食品学院, 河南省郑州市惠济区英才街 8 号,450044 *Email: yaojh@sioc.ac.cn [] 目前, 有机太阳能电池的能量转换效率已经得到较大的提升, 但还不能满足实际应用的要求, 科研人员不断在合成新的化学物质, 以期满足实际应用的要求 已报道的给体 - 受体共聚物 P(BDTn-fDTBT) 和 P(BDTn-DTBT) [2] ( 结构如 Fig. 所示 ) 实验结果显示 :P(BDTn-fDTBT) 和 P(BDTn-DTBT) 聚合物具有较好的光伏性质, 其能量转换效率最高可达 4.4%, 另外其侧链对聚合物物理性质和光伏性质影响较大, 在分子设计中采用合适长度的烷烃做侧链可以兼顾聚合物的可溶性和光伏效率 本文采用量子化学和分子力学方法, 分别计算了 P(BDTn-fDTBT) 和 P(BDTn-DTBT) 聚合物的单分子和材料性质 量子化学计算得到的单分子轨道能级分布图如 Fig. 2 所示, 电荷分布以及紫外可见光谱可定性地解 [2] 释系列聚合物中侧链对聚合物的光伏性质影响机理 采用分子力学方法计算得到了其制成的材料的密度 溶解度参数等材料性质 影响光伏材料的能量转换效率值涉及多种因素, 如 : 聚合物分子的电子跃迁 聚合物分子的侧链结构特征和聚合物材料密度等 本工作的计算和实验结果表明 :P(BDTn-DTBT) 系列聚合物分子的电子跃迁比 P(BDTn-fDTBT) 系列的对提高能量转换效率更有利 ;P(BDTn-fDTBT) 和 P(BDTn-DTBT) 的侧链越长, 材料的能量转换效率值越低 ;P(BDTn-fDTBT) 和 P(BDTn-DTBT) 的材料密度越大, 总体表现为对应材料的能量转换效率值越高 Fig. Molecular Structures of DTBT, fdtbt, Copolymer P(BDT n-dtbt), and P(BDT n-fdtbt) Fig. 2 HOMO and LUMO of fragment models of P(BDT 20-fDTBT) and P(BDT 20-DTBT) 关键词 : 太阳能电池 ; 量子化学 ; 分子力学 ; 能量转换效率参考文献 [] Chang, C.; Cheng, Y.; Hung, S.; Wu, J.; Kao, W.; Lee, C.; Hsu, C. Adv. Mater. 202, 24: 549. [2] Mei, C.; Liang, L.; Zhao, F.; Wang, J.; Yu, L.; Li, Y.; Li, W. Macromolecules 203, 46, 7920. 56

O--0 Nonfitting Protein Ligand Interaction Scoring Function Based on DFT Li RAO,*, Jian WAN, Xin XU 2. Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University,Wuhan, 430079 2 Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Ministry of Education (MOE) Laboratory for Computational Physical Science, Department of Chemistry, Fudan University, Shanghai, 200433 *Email: raoli@mail.ccnu.edu.cn The accuracy of protein-drug binding energy calculation could be improved by the introduction of high level quantum chemistry theories such as density functional theory, but the dramatic computational cost of the combination of DFT and protein means a huge challenge. Such problem could be solved by utilizing the high scale factor of DFT methods reversely. The fragmentation of the protein-drug complex computational system could dramatically reduce the computational cost, as the so called divide & conquer method. However, current literatures mainly focused on the conquer part, i.e. how to calculate the energy of the fragments and add up them to obtain the energy of overall system, while seldomly refer to the same important divide part, or how to fragment the protein drug complex. Lack of a convenient and universal protein drug complex fragment method limited the application of protein drug binding energy divide & conquer computation to case studies, far from wide range application. We have developed a non-empirical protein-drug binding energy calculation method based on two protein-drug complex fragment strategies and the equivalent consideration of calculation accuracy and computational cost. Solvation effect and entropy effect are also obtained quantum mechanically to improve its accuracy and universality. Fig. Calculated non-empirical binding affinity score of 76 CDK2 inhibitors [] vs. experimental data Keywords: Scoring Function; Protein-Ligand Interaction; DFT; XO; QM/MM References: [] L. Rao, I. Y. Zhang, W. Guo, L. Feng, E. Meggers, X. Xu, J. Comput. Chem. 203, 34, 636. [2] L. Rao, B. Chi, Y. Ren, Y. Li, X. Xu,J. Wan. J. Comput. Chem. 206, 37, 336-344. 57

O-- The Allosteric Effects on Protein Induced by Small Ligands Studied by Molecular Dynamics Simulations Mojie Duan *, Na Liu, Yue Guo, Minghui Yang. Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 43007, China *Email: mjduan@wipm.ac.cn The allostery induced by ligands can regulate the protein function and participate in many important biological processes. Allosteric changes are always occurred far away from the ligand binding sites. Understanding the allosteric pathway is important to design novel ligands to manipulate the protein functions. In this study, molecular dynamics simulations were used to study the allosteric effects of ligands to androgen receptor (AR) and fatty acid binding protein (FABP). For AR, we found an allosteric pathway linking ligands and helix 2 (H2) of AR-LBD, which involves the interactions among the ligands and the residues W74, H874, and I899. The interaction pathway provides an atomistic explanation of how ligands affect the structure of AR-LBD. The free energy profiles constructed by the metadynamics simulations revealed the transition process between the antagonistic form and agonistic form of AR-LBD. For FABP, we characterized the structure differences between the apo- and holo-state based on the Markovian state model (MSM). Our studies provide the connections from the ligand binding to the protein function regulations. Keywords: allosteric effects; MD simulations; androgen receptor; fatty acid binding protein References: [] Duan, M., Liu, N., Zhou, W.F., et al. J. Chem. Theory Comput., 206, 2, 46. 58

O--2 危险化学品信息查询系统的建立与应用 徐雯丽, 黄迎, 李佳, 胡静, 蒋舒仰, 李靖靖 2, 姚建华,2* 中国科学院上海有机化学研究所, 上海市零陵路 345 号,200032 2 郑州工程技术学院, 化工食品学院, 河南省郑州市惠济区英才街 8 号,450044 *Email: yaojh@sioc.ac.cn 在化学与化工生产过程中, 化学物质的需求量极大, 其中, 不乏各种类型的危险化学品 根据 危险化学品目录 (205 版 ) [], 危险化学品的定义是指具有毒害 腐蚀 爆炸 燃烧 助燃等性质, 对人体 设施 环境具有危害的剧毒化学品和其他化学品 该目录只包含化学品名称 CAS 号 剧毒性等信息 现有的一些化工类数据库, 例如 chemicalbook [2] chemblink [3], 只提供文字检索, 无化学结构检索功能 这些系统对于与列入目录的化合物属于同系列, 且差别及其微小的化合物, 不能提供任何危化品处理方案和策略的信息 危险化学品信息查询系统 (CISOC-WEBHCIQS) 是具有自主知识产权的 具有化学结构检索功能的网络版危险化学品信息查询系统, 系统结构如 Fig. 所示 该系统提供 6 种检索功能 : 化学结构 CAS 号 英文名称 中文名称 中文别名和毒性 ( 剧毒标记 ) 检索 ( 如 Fig. 2 所示 ) 检索获得的信息包括 : 危险化学品的基本化学信息 ( 中英文名称 CAS 号 化学结构 ), 剧毒标记信息以及化合物的毒性 ( 急性毒性 致癌毒性 致突变毒性 ) 的实验值和预测值 对于无毒性实验报道的化合物而言, 毒性预测值具有它们特定的参考价值, 可以为对应的危险化学品应急处理预案提供参考信息 本信息系统正在扩充事故处理预案信息查询功能 CISOC-WEBHCIQS 是智能技术在化工领域应用的一个实例, 是化工信息平台中不可或缺的一部分, 是化工管理和科研人员提高危险化学品的管理效率与质量的信息系统 Fig. Frame of CISOC-WEBHCIQS Fig. 2 Interface of CISOC-WEBHCIQS 关键词 : 危险化学品 ; 信息查询系统参考文献 [] http://www.chinasafety.gov.cn. [2] http://www.chemicalbook.com/productindex.aspx [3] http://www.chemblink.com/indexc.htm 59

O--3 TargetNet: 多靶点 QSAR 预测潜在的药物 - 靶点相互作用的 在线计算平台董界, 姚志江,*, 曹东升 中南大学湘雅药学院, 长沙市岳麓区桐梓坡路 72 号,40003 *Email: biomed@csu.edu.cn 现代药物开发中, 一个核心问题就是药物 - 靶点相互作用研究 针对药物的药物 - 靶点谱 (DTI profiling) 进行分析能够帮助我们推断药物的适应症, 药物副作用, 药物 - 药物相互作用关系以及药物的作用模式 因此, 在基因组水平上快速可靠地预测药物 - 靶点谱就显得尤为重要 这里, 我们基于多靶点构效关系理论 (Multi-target SAR methodology) 构建了一个能够实时预测药物 - 靶点谱的在线计算平台 :TargetNet 平台核心采用朴素贝叶斯 (Naive Bayes) 方法和多种分子指纹构建了计算速度和准确度俱佳的模型, 并且利用集成的思想构建了这些指纹的集成模型, 提升了整体的预测能力 最终我们得到 623 个模型并进行了多种验证和评估, 得到其整体 AUC 在 75 00 % 之间 使用该平台, 用户只需要提交分子结构文件即可得到该分子通过 623 个高质量构效关系模型后的预测活性, 进而生成该分子的药物 - 靶点谱 该谱可以作为化合物的特征向量应用在多个相关领域 我们已经将其成功应用在药物潜在靶点预测, 药物毒性预测, 药物 - 药物相互作用预测, 药物作用模式预测等方面并展现出强大的预测能力 平台入口 :http://targetnet.scbdd.com 关键词 : 在线预测 ; 药物 - 靶点谱 ;TargetNet;Multi-target SAR 参考文献 [] Cao D-S., Nan Xiao,et al. CPT: pharmacometrics & systems pharmacology, 205, 4(9), 498-506. [2] Yao Z J, Dong J, Cao D-S., et al. J Comput Aid Mol Des, 206, 30(5), 43-424. [3] Dong J, Yao Z J, Zhu M F, Cao D-S., et al. J Cheminformatics, 207, 9():27. 60

O--4 材料机器学习平台 张庆 陆文聪 2,* 上海大学材料学院 上海市宝山区上大路 99 号 200444 上海大学理学院化学系 上海市宝山区上大路 99 号 200444 2 *Email: wclu@shu.edu.cn 随着20年6月材料基因组计划 MGI 的提出 快速开发 制造和部署先进材料 缩短新材料开发周 期 成为了科学家们全球范围内的竞赛[] 机器学习技术在金融 医疗 保险和工业上取得了极大的成功 近年来在材料领域也逐渐取得了令人鼓舞的成果 如 Xue[2]等提出了一种基于机器学习的自适应策略 利 用有限实验样本的机器学习结果预报并实验证实了性能更好的新材料 机器学习技术在近几年中得到了广 泛的发展 但是 应用机器学习算法解决具体材料科学任务需要具有一定的数据分析和计算机专业知识 大量开源的算法包也需要通过python语言才能进行调用 这些不利于材料研究者们直接应用材料机器学习方 法解决其关心的问题 我们实验室以此为出发点 开发了便于材料研究者使用的在线机器学习平台 我们 期望能够最大程度的降低材料研究者们在使用机器学习时的学习成本 使材料设计者能通过直观的图形界 面递交相应的任务 并获取对材料设计有参考意义的结果 在我们的在线机器学习平台中 不仅含有我们自主编写的常用机器学习算法 如 SVM, RVM BPANN PCA等 也有对现今最为优秀的机器学习算法开源包之一Scikit-Learn[3]进行的二次开发 使得用户能够通 过图形界面直接调用其内部的算法 为方便对数据分析不怎么熟悉的材料研究者的使用 平台中的算法均 具有合理的默认参数 计算结果使用图表的形式进行展示 从而给材料研究者提供直观的结果 平台同时 还包括正交实验设计 组内文献传阅和保存等功能 另外 本平台还开放了钙钛矿类材料的虚拟筛选功能 可通过蒙特卡洛算法 同时含有遗传算法和枚 举法按计算量自动切换 自动生成海量的虚拟数据 使用平台中已经建立的QSPR模型进行虚拟筛选 最终 为材料研究者提供符合要求的候选材料 Fig. UI of WebService for Perovskite Machine Learning 关键词 Machine Learning Perovskite WebService 参考文献 [] Materials Genome Initiative for Global Competitiveness. Coucil, N. S. a. t., Ed. Washington D.C.: America, 20. [2] Xue, D.; Balachandran, P. V.; Hogden, J.; Theiler, J.; Xue, D.; Lookman, T., Accelerated search for materials with targeted properties by adaptive design. Nat. Commun. 206, 7, 24. [3] Scikit-learn: Machine Learning in Python, Pedregosa et al., JMLR 2, pp. 2825-2830, 20. 6

O-2-0 一种用于复杂样品光谱信号的选择性集成预处理方法研究 第五鹏瑶 卞希慧* 初园园 谭小耀 天津工业大学 省部共建分离膜与膜过程国家重点实验室 环境与化学工程学院 天津 300387 *Email: bianxihui@63.com 复杂样品光谱数据会受到杂散光 噪声 基线漂移等因素的干扰 从而影响定性定量分析结果 因此 在 建模之前往往需要对数据进行预处理[] 由于杂散光 噪声 基线漂移等干扰可能同时存在 单一的预处理 方法不能消除多种因素的影响 需要对预处理方法进行组合 在组合预处理中 预处理方法的数目和顺序 都会影响预测结果 尽管有研究表明 预处理方法按照基线校正 散射校正 平滑和尺度缩放的顺序组合 效果较好[2] 但是单一的预处理方法有十几种 它们之间的组合方式有上百种 不同样品不同仪器测得的光 谱数据的最佳预处理方法也都不同 因此 对于被分析的光谱数据 如何选择最佳的预处理方法是很棘手 的工作 集成技术不选取最佳的方法 而是考察多种方法 对多种方法的结果融合得到一个最终结果[3] 本研究将集 成技术与预处理方法相结合 然后把无预处理及一阶导数 二阶导数 连续小波变换 多元散射校正 标 准正态变量 SG 平滑 中心化 最大最小归一化 标准化等 0 种预处理方法按照基线校正 散射校正 平滑和尺度缩放的顺序进行全排列组合得到 20 种预处理及其组合方法 分别建立 PLS 模型 选择预测效 果优于无预处理-PLS 模型的预测结果进行集成 其简单平均作为最终预测结果 采用玉米 血液 三元混 合物 食用油 4 组数据进行实验 并与无预处理-PLS 集成预处理-PLS 进行比较 如图 所示 结果表明 选择性集成预处理不仅避免了预处理方法的选择 并能获得与最佳预处理方法相当或更好的预测效果 图 选择性集成预处理PLS 红 集成预处理PLS 绿 预处理PLS 蓝 和PLS 玫红 预测的预测均方根误差图 (a) 玉 米数据, (b) 血液数据, (c) 三元混合物数据, (d) 食用调和油数据 关键词 预处理 偏最小二乘 集成 光谱分析 致谢 本研究受国家自然科学基金委项目 编号 24050和260360 的经费支持 参考文献 [] Xu, L.; Yan, S. M.; Cai, C. B.; Yu, X. P.; Jiang, J. H.; Wu, H. L.; Yu, R. Q. Anal. Chim. Acta. 2008, 66: 38. [2] Gerretzen, J.; Szymanska, E.; Jansen, J. J.; Bart, J.; van Manen, H. J.; van den Heuvel, E. R.; Buydens, L. M. C. Anal. Chem. 205, 87(24): 2096. [3] Bian, X. H.; Li, S. J.; Shao, X. G.; Liu P. Chemom. Intel. Lab. Syst. 206, 58: 74. 62

O-2-02 利用温控近红外光谱研究水在蛋白质水凝胶形成过程中 的作用 * 马丽, 蔡文生, 邵学广 南开大学化学学院, 分析科学研究中心, 天津卫津路 94 号,30007 *Email: xshao@nankai.edu.cn 近红外光谱对水分子的 OH 基团非常敏感, 在不同温度下, 具有不同氢键结构的 OH 基团会呈现不同的变化, 包含了丰富的物理化学信息, 因此温控近红外光谱对研究水分子的氢键网络有独特的优势 本课题组也成 [] 功利用温控近红外光谱对生物大分子水溶液中的氢键网络进行过研究, 解释了葡萄糖对生物水环境的作用 [2] 和蛋白质水溶液中蛋白质的结构以及水合作用变化 蛋白质水凝胶是一种典型的能够吸收大量水的蛋白质聚集体, 水在它形成的过程中起到了重要的作用 利用温控近红外光谱不仅可以从微观角度研究不同水团簇对蛋白质水凝胶的作用, 还可以对凝胶形成的过程进行实时监测, 为制备性能更好的蛋白质水凝胶提供理论依据 本文以卵清蛋白为例, 研究球蛋白水溶液形成凝胶过程中水组成的变化, 分析水在这个过程中的作用 通过测定 30-90 温度范围内卵清蛋白水溶液的近红外光谱, 使用高斯拟合的方法从水的吸收峰中提取出了 5 种不同结构的水团簇的特征光谱, 并对其特征光谱的强度随温度的变化进行分析, 结果表明, 每种水团簇随温度变化的转折点和蛋白质的结构变化 [3] 的转折点相同 进一步利用二维相关光谱分析每种水团簇的先后变化顺序, 结果表明, 含有两个氢键的水团簇在球蛋白形成凝胶的过程中促进了凝胶结构的形成, 并维持凝胶结构的稳定 关键词 : 近红外光谱 ; 蛋白质水凝胶 ; 水团簇 ; 高斯拟合 ; 二维相关光谱 参考文献 [] Cui, X.Y.; Cai, W.S.; Shao, X.G. RSC Adv. 206, 6(07): 05729. [2] Fan, M.L.; Cai, W.S.; Shao, X.G. Appl Spectrosc. 207, 7(3): 472. [3] Noda, I. Appl Spectrosc. 993, 47(9): 329. 国家自然科学基金项目 (No. 2475068) 资助 63

O-2-03 基于近红外光谱的温度效应同时定量分析混合物中的三种成分 刘金金, 李保琼, 徐敏莉, 王雪, 翟红林 *,Jules Muhire 兰州大学化学化工学院, 兰州,730000 *Email:zhaihl@lzu.edu.cn 在近红外光谱常规分析中, 温度效应通常被看作一个干扰因素 在本研究中, 基于原始的近红外光谱的温度效应, 利用 Tchebichef image moment 方法对混合物中的三种成分同时进行定量分析 通过将温度参数作为一个重要维度来构建三维光谱图, 提供了更丰富的样品信号, 为定量分析提供了客观 全面 准确的信息 将三维光谱图转换为灰度图后, 利用 Tchebichef image moment 的平移 旋转 缩放不变性及多分辨率的特性, 以不同阶数下得到的 Tchebichef moments 作为自变量, 用逐步回归来建立三种成分的定量模型 定量模型的留一法交互检验的相关系数高于 0.9952, 预测的相关系数高于 0.9926, 与传统的偏最小二乘法相比,TM 对于多组分的同时定量分析具有简单 准确 可靠等优势 该研究表明,TM 可以有效克服近红外光谱的温度效应, 获得较好的定量分析结果 B Fig: (A) The NIR 3D spectrum of one sample under five different temperatures. (B) The plots of experimental vs. calculated concentration for three target components. 关键词 : 近红外光谱 ; 温度效应 ; 定量分析 ; 图像矩参考文献 [] Shan, R.; Zhao, Y.; Fan, M.; Liu, X.; Cai, W. S.; Shao, X. G. Talanta. 205, 3: 70. [2] Shao, X. G.; Kang, J.; Cai, W. S. Talanta. 200, 82: 07. [3] Wojtkow, D. and Czarnecki, M. A. J. Phys. Chem. A. 2006, 0: 0552. [4] Zhai, H. L.; Zhai, Y. Y.; Li, P. Z.; Tian, Y. L. Analyst. 203,38: 683. [5] Li, B. Q.; Xu, M. L.; Wang, X.; Zhai, H. L.; Chen, J.; Liu, J. J. Food Chem. 207, 26: 52. [6] Li, B. Q.; Chen, J.; Xu, M. L.; Wang, X.; Zhai, H. L. Chemom. Intell. Lab. Syst. 206, 56: 28. 64

O-2-04 三维温控近红外光谱数据的多级成分分析 崔晓宇, 蔡文生, 邵学广 * 南开大学化学学院, 分析科学研究中心, 天津,30007 *Email: xshao@nankai.edu.cn 近红外光谱不仅包含了物质结构的信息, 而且包含了分子内或分子间相互作用的信息 温度变化会导致相互作用发生变化, 进而引起光谱的变化 温控近红外光谱数据包含了物质含量和结构变化的信息, 因此可以用于定量分析和结构分析 在定量分析方面, 本课题组建立了温度 - 光谱定量分析 (QSTR) 模型, 并以此为 [-3] 基础, 预测了溶液的组成 然而, 简单的模型无法分别得到温度和浓度的信息 为了区分温度和浓度信 [3] 息, 研究了多级同时成分分析 (MSCA) 算法对温控近红外光谱数据分析能力 MSCA 方法能够在不同层次分析数据, 并且分别考察数据内温度和浓度对光谱成分的影响 利用 MSCA 分层解析的特点, 分别建立了温度间模型和温度内模型 采用温度间模型得到的温度系数建立了 QSTR 模型 ; 采用温度内模型得到的浓度系 [4] 数预测了溶质的组成 进一步利用 MSCA 算法可增强模型解释性的特点, 进行结构分析, 对葡萄糖水溶液的温控近红外光谱进行了解析 从温度间模型的结果中可以得出随温度升高, 水分子中自由 OH 的含量增加, 小的水团簇含量先增加后减少, 大的水团簇逐步解离, 证明了升温过程中不同水结构相互转化的过程 ; 温度内模型结果表明葡萄糖易与小的水团簇相互作用, 并促进了水中稳定的四面体结构的生成, 解释了葡萄糖在生命体系中的作用 关键词 : 近红外光谱 ; 温度 ; 水 ; 多级同时成分分析 参考文献 [] Shao, X.G.; Kang, J.; Cai, W.S. Talanta 200, 82: 07. [2] Kang, J.; Cai, W.S.; Shao, X.G. Talanta 20, 85: 420. [3] Cui, X.Y.; Cai, W.S.; Shao, X.G. RSC Adv. 206, 6: 05729. [4] Timmerman, M.E. Br. J. Math. Stat. Psychol. 2006, 59: 30. [5] Shan, R.F.; Zhao, Y.; Fan, M. L.; Liu, X.W.; Cai, W.S.; Shao, X.G. Talanta 205, 3: 70. [6] Cui, X.Y.; Liu, X.W.; Yu, X.M.; Cai, W.S.; Shao, X.G. Anal. Chim. Acta 207, 957: 47. 国家自然科学基金项目 (No. 2475068) 资助 65

O-2-05 水分子跨越纳米通道及生物膜的输运性质 苏加叶,*, 赵云震, 方昶, 吕福静 南京理工大学, 南京市孝陵卫 200 号,20094 *Email: jysu@iccas.ac.cn 水是构成生命物质的基础, 水的输运不仅与人类的生产生活息息相关, 如水在各种管道中的输运, 药物溶液的注射, 毛吸现象等等 ; 而且对生物体的新陈代谢至关重要 在生物体内, 水分子跨越细胞膜通常是由膜上的水通道蛋白控制 []; 另一方面, 一些典型的计算机模拟 [2] 和实验 [3,4] 研究表明水分子能够快速的穿越孔径为 nm 左右碳纳米管, 而水中的离子却不能轻易通过, 这为高效 低能耗过滤膜的设计提供了新思路, 有望能应用在污水处理以及海水淡化等方面 溶液中不同种类的离子与水分子具有不同的相互作用, 因而离子的种类及浓度对离子及水分子跨膜输运过程必将产生重要的影响 我们最近的计算机模拟研究发现 [5], 水分子与阴离子的耦合作用要明显比阳离子强, 因此阴离子的输运性质决定了水分子的输运行为, 在一定程度上揭示了水分子和离子的耦合输运过程, 对离子的过滤与分离具有一定的参考意义 此外, 细胞在盐溶液中由于渗透压驱动会发生水分子的跨膜输运, 这对细胞形状的演化具有重要的影响 我们以囊泡为模型 [6], 如图 所示, 设计了盐溶液在囊泡内部和外部两种情况, 并惊奇的发现, 这两种情况下水分子跨膜输运行为具有高度的不对称性, 这主要是由于磷脂 - 离子, 磷脂 - 水, 磷脂 - 磷脂之间相互作用的不对称性 Fig. Simulation snapshots for water transport through a vesicle membrane. 关键词 : 水分子 ; 输运 ; 通道 ; 囊泡参考文献 [] De Groot, B. L.; Grubmuller, H. Science 200, 294: 2353. [2] Hummer, G.; Rasaiah, J. C.; Noworyta, J. P. Nature 200, 44: 88. [3] Holt, J. K.; Park, H. G.; Wang, Y. M.; et al. Science 2006, 32: 034. [4] Secchi, E.; Marbach, S.; Nigues, A.; et al. Nature 206, 537: 20. [5] Su, J. Y.; Huang, D. C. J. Phys. Chem. C 206, 20: 245. [6] Su, J. Y.; Zhao, Y. Z.; Fang, C.; Shi, Y. J. Chem. Phys. 207, 46: 204902. 66

O-2-06 核酸适配体的计算机模拟研究 周庆同,Eugene Shakhnovich 2, 赵素文 *, 梁好均 3* 上海科技大学 ihuman 研究所, 上海市浦东新区海科路 99 号,2020 2 Harvard University, 2 Oxford Street, Cambridge MA 0238 3 中国科学技术大学高分子科学与工程系, 安徽省合肥市金寨路 96 号,230026 *Email: zhaosw@shanghaitech.edu.cn; hjliang@ustc.edu.cn; 核酸适配体是一类能高亲和 强特异识别靶标的短链 DNA 或 RNA 自 990 年核酸适配体被发现 [-2], 已有大量研究报道核酸适配体的实验筛选方法及结果和基于核酸适配体的生物化学传感器, 但核酸适配体的靶标识别机制研究却相对不足, 核酸 - 靶标作用体系的物理特征仍不明晰, 核酸适配体的序列优化设计问题尚待解决, 这限制核酸适配体的广泛应用 为解决核酸适配体的序列优化问题, 我们从计算机模拟的角度出发研究核酸适配体的序列 - 结构 - 功能关系, 提出 SELEX in silico 方法 [3-4] 实现核酸适配体的理性优化设计 SELEX in silico 方法的第一步是基于二级结构预测的序列筛选, 目的是寻找到那些能以较低代价形成目标二级结构的核酸序列, 组成增强型初始序列库, 第二步是基于分子动力学模拟和结合自由能计算的虚拟筛选, 在原始核酸适配体 - 配体复合物的三维结构基础上我们进行序列突变得到突变体的假定结合构象, 使用分子动力学模拟考察假定的结合构象是否稳定, 小分子是否离开, 小分子 - 核酸的结合自由能是多少, 从而筛选得到具有较好靶标亲和力的核酸序列 我们以茶碱适配体 [3] 和精氨酰胺适配体 [4] 为研究对象, 使用 SELEX in silico 筛选获得数十种具有更强靶标亲和力的 全新核酸适配体, 揭示了核酸的序列 - 结构 - 功能关系的复杂多样, 拓展了计算模拟方法在核酸等生物大分子研究的应用 Fig. Two novel L-argininamide binding aptamers identified by SELEX in silico. 关键词 : 核酸适配体, 序列 - 结构 - 功能关系, 序列空间,SELEX in silico, 分子动力学模拟 参考文献 [] Ellington, A. D.; Szostak, J. W. Nature 990, 346 (6287), 88-22. [2] Tuerk, C.; Gold, L. Science 990, 249 (4968), 505-0. [3] Zhou, Q.; Xia, X.; Luo, Z.; Liang, H.; Shakhnovich, E. J Chem. Theory Comput. 205, (2), 5939-46. [4] Zhou, Q.; Sun, X.; Xia, X.; Fan, Z.; Luo, Z.; Zhao, S.; Shakhnovich, E.; Liang, H. J Phys. Chem. Lett. 207, 8 (2), 407-44. 67

O-2-07 Cholesteric Ordering in Coarse-grained Polymeric Molecule with Helical Interaction Liang Wu, Huai Sun,* School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240 *Email: huaisun@sjtu.edu.cn Understanding of cholesteric liquid crystals from molecular level is challenging. Limited insights are available to bridge between molecular structural information and macroscopic chiral organization. In present study, we introduce a novel coarse-grained (CG) polymeric molecular model, namely flexible chain particle with helical interactions (FCh, Fig. a) to simulate the liquid crystalline phase behaviour of generic cholesteric molecular systems such as double strand DNA and α-helix polypeptide. Molecular dynamics simulation are performed to study the isotropic-cholesteric phase transition of FCh molecules with varying intramolecular flexibilities. We use wall confinement to break system symmetry along the cholesteric helix director and calculate the equilibrium cholesteric pitch. The FCh molecular system shows stable left-handed cholesteric phase in bulk region in the right-handed FCh model (See Fig. b). We also observe the spatial inhomogeneous distribution of nematic order parameter profile in cholesteric phases. The molecular flexibility plays a necessary role in determining the macroscopic cholesteric pitch. Our simulation provides some guidelines for CG modelling general cholesteric liquid crystals and chiral molecular systems. Fig. (a) Coarse-grained molecular model for cholesteric LCs: flexible chain particle with helical interactions (FCh) model. Fig. 2 upper: snapshot of cholesteric state; lower: (a) periodic distribution of twist angle profile, (b) long range orientational correlation in cholesteric phase Keywords: Cholesteric, Liquid crystal polymer, Molecular dynamics, Coarse graining References: [] C. Greco, A. Ferrarini. Phys. Rev. Lett. 205, 5: 4780. [2] S. Dussi, M. Dijsktra. Nature. Comm. 206, 7: 75 68

O-2-08 Chiral self-assembly of phenylalanine molecules on Au() Ping Cheng, Hui Wang, Xinghua Shi,* National Center for Nanoscience and Technology, No. Beiyitiao, Zhongguancun, Beijing, China, 0090 First principle density functional theory calculations are used to study the chiral self-assembly of phenylalanine on Au(). Phenylalanine molecules have two chiral structures, which are also two enantiomorphous configurations, i.e. L-phenylalanine and D-phenylalanine. At a low coverage of /3 monolayer (ML), L-phenylalanine or D-phenylalanine molecule forms bonds with Au atoms of Au(), and the adsorption energy is -3.8 ev/molecule for L-phenylalanine and -3.7 ev/molecule for D-phenylalanine. At high coverage of ML, the phenylalanine molecules not only bond with Au atoms of Au(), but also can form hydrogen-bonded networks with other phenylalanine molecules around them. At ML, the adsorption energy of L-phenylalanine and D-phenylalanine are both -3.45 ev/molecule, which is higher than those of /3 ML. This result indicates that the hydrogen-bonds are benefit for the stability of the interaction systems. Moreover, At ML, four adjacent L-phenylalanine or D-phenylalanine molecules can self-assemble to form chiral windmill-like patterns through their benzene rings, and seven adjacent L-phenylalanine or L-phenylalanine molecules can self-assemble to form a chiral flower-like pattern with one phenylalanine in the middle acting as the stamen, and other six phenylalanine molecules acting as petals. Keywords: chirality; self-assembly; DFT calculation; phenylalanine; 69

O-2-09 Ensemble strategies and methods for the spectral quantitative analysis of complex samples Xihui Bian *, Pengyao Diwu, Xiaoyao Tan, Yugao Guo State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin, 300387, P. R. China *Email: bianxihui@63.com Ensemble strategies have gained increasing attention in multivariate calibration for quantitative analysis of complex samples []. The aim of ensemble calibration is to obtain a more accurate, stable and robust prediction by combining the predictions of multiple sub-models [2]. The generation and calibration of the training subsets, as well as the integration of the sub-models are three keys to the success of ensemble calibration. Many training subset generating and sub-model integrating strategies have been developed to form numerous ensemble calibration methods for improving the performance of the basic calibration method. The training subset generation strategies include generating subsets from sample direction, variable direction, double directions, and transforming the original signal by mathematical transformation techniques. Fig. 2(a) shows that the generation of training subsets from sample direction is the frequently used strategies. In the sub-model calibration algorithm aspect, all single multivariate calibration methods can be used theoretically, such as MLR, PCR, PLS, SVR, ANN, ELM, etc. Among them, PLS is the most widely applied basic calibration algorithm, as seen in Fig. 2(b). The integrating strategies include ensemble and selective ensemble integration. Ensemble integrating strategies can be further divided into selecting, combining and unfolded strategies [3]. From Fig. 2(c), the most commonly used integration strategy is the weighted average. This contribution focuses on the above-mentioned ensemble strategies in relation to calibration of complex samples. The limitations and perspectives of these ensemble strategies are also discussed. Fig. The number of references for different training subset generating strategies (a), basic calibration algorithms for sub-models (b) and sub-model integrating strategies (c) Keywords: Ensemble modeling; Multivariate calibration; Spectral analysis; Complex samples Acknowledgements: This study is supported by the National Natural Science Foundation of China (No. 24050) References: [] Laborda, F.; Bolea, E.; Cepria, G.; et al. Anal. Chim. Acta 206, 904: 0-32. [2] Li, Y.K.; Shao X.G.; Cai W.S. Talanta. 2007, 72(): 27-222. [3] Bian, X.H.; Li, S.J.; Lin, L.G.; et al. Anal. Chim. Acta 206, 925:6-22. 70

O-2-0 基于集群分析的化学建模相关算法研究云永欢,2,*, 李勤奋,2, 梁逸曾 3 中国热带农业科学院环境与植物保护研究所, 海南省海口市,570 2 农业部儋州农业环境科学观测实验站, 海南省海口市,570 5 中南大学化学与化工学院, 湖南省长沙市,40083 *Email: yunyonghuan@foxmail.com 化学计量学和化学信息学研究的一个重要目标是建立一个有效并可靠的化学模型, 以对未知的化学样本的浓度 / 性质等进行准确预测 由于模型 f(.) 为完全未知的软模型, 不确定性很高 而任何软模型的建立依赖于数据, 因而受到了样本和变量的影响 数据决定了软模型建立的上限, 而模型和算法只是逼近这个上限而已 实际研究中, 对于有限的样本, 采用单个方法建立的单个模型, 由于方法和数据的局限性, 其仅仅是反映了数据的某个侧面, 使得结果的可靠性带来不确定性 集群分析 (Population Analysis) 是解决此类问题的有效办法 集群分析通过结合多个模型 多个角度以及多个方法来分析, 旨在于打破传统一次性分析的思路, 即采用集群的思路, 强调结合利用或统计分析所得的各种不同结果, 与一次性分析形成了强烈对比 集群分析包括模型集群分析和方法集群分析 模型集群分析 [] 是由 Li 等人于 200 年提出的化学建模算法构建框架思路, 其力求最大限度地利用已有样本集的信息, 通过随机采样, 从不同角度来考察数据集的内在性质, 多个视点看待化学建模, 并通过多次建模以尽量逼近建模基空间, 以避免模型的过拟合或其他建模陷阱, 继通过对所得结果进一步统计分析而获得数据集的内在结构 方法集群分析 [2] 是由 Yun 等人新近提出的通过结合利用多种非建模或建模方法得出的不同结果来作进一步的分析, 是对集群分析的一个补充和扩展 需要注意的是, 模型集群分析强调的是选定某种方法对从数据的子空间获取的子数据集建立的子模型群来分析问题, 是一种基于各个子模型的分析思路 而方法集群分析强调的是结合利用各个方法应用于原数据获得结果来分析问题, 是一种基于各个方法所得结果的分析思路 图 表示了集群分析的简单框架 目前, 基于模型集群分析的化学建模算法研究已成功应用在奇异值诊断 [3], 变量选择 [4-6], 模型参数优化 [7] 以及模型应用域 [8], 方法集群分析也已应用在代谢组学的生物标记物挑选上 [9] Fig. The Framework of population analysis 关键词 : 集群分析 ; 化学建模 ; 变量选择 ; 模型应用域 参考文献 [] Li, H-D; Liang, Y-Z*; Cao D-S; Trac-Trend. Anal. Chem. 202, 38: 54. [2] Yun, Y-H; Deng, B-C; Cao D-S; Wang, W-T; Liang, Y-Z*. Anal. Chim. Acta. 206, 9: 27. [3] 云永欢, 邓百川, 梁逸曾 *. 分析化学, 205, 43: 638. [4] Yun, Y-H; Wang, W-T; Liang, Y-Z*; Cao D-S; Lu, H-M; Xu. Q-S. Anal. Chim. Acta. 204, 807: 36. [5] Yun, Y-H; Wang, W-T; Deng, B-C; Liang, Y-Z*; Fan, W; Xu. Q-S. Anal. Chim. Acta. 205, 862: 4. [6] Yun, Y-H; Fu, L; Deng, B-C; Lu, H-M;Yan, J; Yi, L-Z; Liang, Y-Z*. Metabolomics, 205, : 539. [7] Deng, B-C; Yun, Y-H; Liang, Y-Z*; Cao D-S; Yi, L-Z; Xu. Q-S. Anal. Chim. Acta. 205, 880: 32. [8] Yun, Y-H; Cao D-S; Xu, Q-S. Chemometr. Intell. Lab. Syst. In revision. 7

O-2- 多元校正方法在临床复杂样本定性与定量分析中的应用 文志宁, 柳媛, 谢凡凡, 梁羽, 郝颖异, 李梦龙,* 四川大学化学学院, 成都市一环路南一段 24 号, 邮编 :60065 *Email: liml@scu.edu.cn 作为化学计量学中的一类重要方法, 多元校正与分辨方法不仅在分析化学邻域有着广泛的应用, 并已成功用于食品科学以及环境科学的定性 定量分析当中 然而, 在临床样本分析方面, 由于受到临床样本的复杂性以及样本收集不易等的限制, 还未能得到有效应用 因此, 为了推进该类方法在临床诊断及疾病预后预测中的应用, 我们在研究当中针对临床样本的光谱数据和基因组学数据, 提出了一系列基于多元校正的算法用于定性 定量分析 在定性分析中, 我们尝试了多种特征筛选方法, 如 VCPA 等, 可有效从口腔组织样本的拉曼光谱中选取特征点, 并结合机器学习方法, 用于正常组织 口腔白斑以及口腔鳞状细胞癌的快速分类识别 在定量分析中, 我们采用非负矩阵分解算法以及后修正的非负矩阵分解算法, 可有效利用临床样本的基因表达数据, 计算出其中混杂的多个细胞类型的含量及纯细胞的基因表达谱 该类方法不仅可在寻找疾病相关基因时获得更多潜在的候选基因, 并且在缺少校正样本的情况下能够更好的对细胞含量进行估计, 更适合于临床定量分析 综上所述, 多元校正与分辨方法能有效辅助临床快速诊断以及对疾病可能的过程及结果进行预测, 随着检测手段的飞速发展, 该类方法在临床复杂样本分析方面必将获得更为广泛的应用 关键词 : 临床样本 ; 多元校正 ; 基因组学数据 ; 拉曼光谱 ; 定性与定量分析参考文献 [] Liu Y., et al., J Chemometr., 207, In press. [2] Huang L., et al., Anal. Methods, 205, 7, 590. [3] Li Y., et al., J. Raman Spectrosc., 200, 4, 42-47. [4] Zhang J., et al., Chemom. Intell. Lab. Syst., 203, 26, 00-07. 致谢感谢国家自然科学基金 (NO. 2575094,NO. 26754) 对该工作的支持 72

O-2-2 一类偏最小二乘法 : 算法 工具包与应用 徐路 * 铜仁学院材料与化学工程学院, 铜仁,554300 *Email: lxchemo@63.com 最近提出了用于多元质量控制的一类偏最小二乘法 (OCPLS) 根据 OCPLS 的得分距离 (SD) 和绝对中心化残差 (ACR), 可将一个新样品归于以下四类 : 正常值, 类奇异值, 好杠杆点和坏杠杆点 同时发展了 OCPLS 的 MATLAB 工具包, 包括常规 非线性和稳健 OCPLS 算法 分别基于高斯径向基函数和偏稳健 M- 回归方法设计了非线性和稳健 OCPLS 算法 OCPLS 已被成功用于多种道地食品掺杂假冒的无目标检测 关键词 : 一类偏最小二乘法 ; 无目标检测 ; 食品掺杂与假冒参考文献 [] Xu, L.; Yan, S.-M.; Cai, C.-B.; Yu, X.-P. Chemom. Intell. Lab. Syst. 203,26:. [2] Xu, L.; Goodarzi, M.; Shi, W.; Cai, C.-B.; Jiang, J.-H. Chemom. Intell. Lab. Syst. 204,39: 58. [3] Xu, L.; Ye, Z.-H.; Yan, S.-M.; Shi, P.-T.; Cui, H.-F.; Fu, X.-S.; Yu, X.-P. Anal. Chim. Acta 202,754: 3. [4] Xu, L.; Yan, S.-M.; Cai, C.-B.; Yu, X.-P. Food Chem. 203,4: 432. [5] Xu, L.; Shi, P.-T.; Ye, Z.-H.; Yan, S.-M.; Yu, X.-P. Food Chem. 203,4: 2434. [6] Fu, H.-Y.; Li, H.-D.; Xu, L.; Yin, Q.-B.; Yang, T.-M.; Ni, C.; Cai, C.-B.; Yang, J.; She, Y.-B. Food Chem. 207,227: 322. 73

O-2-3 基于化学计量学的两种总植物碱测定方法的一致性研究 李跑,*, 杜国荣 2 湖南农业大学食品科学技术学院, 湖南长沙,4028 2 上海烟草集团有限责任公司技术中心北京工作站, 北京,02 *Email: lipao@live.cn 联合 0 家共同实验室, 对 8 个烟草样品分别用水和乙酸萃取 用连续流动 ( 硫氰酸钾 ) 法 (NM 法 ) 替代高毒性氰化钾法 (CRM35 法 ) 提取总植物碱,8 个烟草样品的总植物碱含量为.00%~5.00% 使用重现性和再现性 配对 T 检验 Bland Altman Passing Bablok 回归方法, 对 0 个实验室的检测数据进行比对 结果表明相同萃取条件下,CRM35 NM 检测结果的相对偏差小于 3.00%; 不同萃取条件下,CRM35 和 NM 检测结果的相对偏差小于 4.00%, 水萃取体系结果略高 ; 使用配对 T 检验方法比对不同实验室的检测值呈现不一致性结果, 需要其他方法辅助进行分析 ;Bland Altman 法结果表明,4 种比较方式下, 方法之间的结果都是一致的, 不同萃取条件下的结果需要经过线性回归校正 ; 使用 Passing Bablok 法得出了不同萃取条件下, 结果之间的线性关系, 可以通过该法实现不同萃取体系结果的相互转化 Fig. Bland Altman results 关键词 : 总植物碱 ; 配对 T 检验 ;Bland Altman 法 ;Passing Bablok 法参考文献 [] Islam, K. M.; Schweigert, F. J. Food Chem. 205, 72: 233. [2] 张杰, 马雁军, 石睿, 张威, 马莉, 王颖, 周骏. 硫氰化钾与 DCIC 反应法测定烟草总植物碱. 烟草科技, 204(5): 60. 74

O-2-4 振动光谱探针用于多肽构象态特征研究 郑轩,2, 刘佳,2, 蔡开聪,2,* 福建师范大学, 化学与化工学院, 福建福州,350007 2 福建省理论与计算化学重点实验室, 福建厦门,36005 * Email: ckc7@fjnu.edu.cn 组织中特定蛋白质如果发生错误折叠, 将会发生自组装形成难溶的纤维聚集体在脑部沉积, 引发如阿尔茨海默病 II 型糖尿病等 蛋白质构象病 蛋白质错误折叠所导致的构象病给社会公共卫生带来了严峻的压力, 研究蛋白质错误折叠机制对疾病的认识与治疗具有重要意义 本文借助分子动力学模拟及振动光谱探针研究溶液相中阿尔茨海默病的致病因子 β- 淀粉样蛋白 (Amyloid β protein, Aβ) 的动态结构及酰胺 -I 带 [-3] 光谱特征 多肽骨架酰胺 -I 带具有二级结构敏感性, 且常常在中红外区形成一个特征的吸收带 借助多肽骨架酰胺光谱表象, 可以帮助我们从分子水平上理解 Aβ 蛋白结构变化特征 本文开展 Aβ25-35 片段中氨基酸模型二肽在液相中的分子动力学模拟, 等间隔选取轨迹中的瞬态结构作为建模样本, 计算溶剂分子与二肽骨架投影于酰胺单元产生的静电势, 结合 DFT 计算得到二肽分子气相酰胺 -I 带频率随二级结构变化的特征来考察可能存在的振动耦合 将酰胺单元原子位点上的静电势场和具有二级结构依赖性的气相酰胺 -I 带频率结合在一起, 使各个模型二肽分子气 / 液相频率差相关联, 通过超定方程拟合得到一套静电频率转换参数, 分别构建具有普适性和氨基酸特异性的酰胺 -I 带频率图 将参数应用于 [4] Aβ25-35 多肽体系的全原子运动轨迹中, 得到优化后的酰胺 -I 带频率分布, 较好地重现了实验光谱 ( 重叠率 95%), 分子动力学轨迹统计结果 ( 图 A) 与模拟光谱 ( 图 B) 均表明该多肽片段在溶液中倾向形成 β- 折叠结构 Fig. Probability of summarized backbone dihedrals distribution ( ) of Aβ25-35 in D2O (panel A), and static frequency distributions of amide-i band (panel B). 关键词 : β- 淀粉样蛋白, 振动光谱, 酰胺 -I 带, 二级结构, 分子动力学模拟参考文献 [] Kraack, J. P.; Hamm, P. Chem. Rev. 207, 7: 0623. [2] Bondarenko, A. S.; Jansen, T. L. C. J. Chem. phys., 205, 42: 22437. [3] Kim, H.; Cho, M. Chem. Rev. 203, 3: 587. [4] Guo Y.; Wang J. ChemPhysChem, 202, 3: 390. 75

O-2-5 银镜基质用于近红外漫反射光谱定量血清中总胆红素的 研究 * 王舒瑜, 张进, 蔡文生, 邵学广 南开大学化学学院分析科学研究中心, 天津,30007 *Email: xshao@nankai.edu.cn 近红外光谱分析技术以其快速 无损和无需预处理等特点被广泛应用在食品 卫生 石油等领域 随着化学计量学的发展, 该技术逐渐被用于临床疾病诊断的研究 采用近红外透射分析技术, 借助于多元校正方法建立化学信息值和光谱之间的定量模型, 研究人员已经成功对血清中葡萄糖 蛋白 尿素 甘油三酯 [,2] 胆固醇等多种生化指标进行了测定 然而, 透射光谱中水的吸收干扰较强, 导致一些微量组分的信息被掩盖, 使得该技术局限于对血清中常量物质的分析检测 以漫反射的形式采集干燥后固体样品的光谱, 可以避免水分的干扰 此外, 本课题组提出利用低背景吸收材料的富集技术与近红外漫反射分析技术相结合, [3,4] 实现复杂基质中微量组分的定量检测 其中, 利用银的低背景吸收和强反射性质, 对其表面富集的溶菌 [5] 酶实现了高灵敏的检测 本文同样采用银镜作为基底物质, 应用近红外漫反射光谱技术, 实现了对血清中微量总胆红素的定量测定 该方法先制作带有凹槽阵列的银镜基底, 将血清样品滴加在凹槽内, 待其水分蒸发后, 直接采集干燥后血 [6] 清的近红外漫反射光谱 使用 SVR 非线性拟合方法, 结合 MC-UVE 筛选变量, 对未稀释的血清样品中微量的总胆红素进行定量研究 该方法不仅提高了检测的灵敏度, 也为临床定量血清中微量组分提供了一种分析手段 关键词 : 银镜 ; 近红外漫反射光谱 ; 血清 ; 总胆红素参考文献 [] Hazen K.H.; Arnold M. A.; Small G. W. Anal. Chim. Acta, 998, 37: 255. [2] Garcia Garcia J. L.; Pérez Guaita D.; Ventura Gayete J.; Garrigues S.; de la Guardia M. Anal. Methods, 204, 6: 3982. [3] Cui, C.J.; Cai, W.S.; Shao, X.G. Chinese Chem. Lett., 203, 24: 67. [4] Wang, C.C.; Cai, W.S.; Shao, X.G. J. Near Infrared Spectrosc., 206, 24: 345. [5] Wang, C.C.; Wang, S.Y.; Cai, W.S.; Shao, X.G. Talanta, 207, 62:23. [6] Cai, W.S.; Li, Y.K.; Shao, X.G. Chemometr. Intell. Lab. 2008, 90: 88. 国家自然科学基金项目 (No. 2475068) 资助 76

O-2-6 基于温控近红外光谱和独立成分分析研究寡肽的水合作用 程丹, 蔡文生, 邵学广 * 南开大学化学学院, 分析科学研究中心, 天津南开区卫津路 94 号,30007 *Email: xshao@nankai.edu.cn 寡肽作为蛋白质的片段和结构单元, 已经被广泛用作模型来研究蛋白质的性质 研究寡肽的水合作用有助于我们进一步了解蛋白质在水溶液中的性能 本文利用温控近红外光谱结合独立成分分析, 以水分子为探 [] 针研究寡肽 Asp-Asp-Asp-Asp-Asp(D5) 在水溶液中的水合作用 采集不同浓度的寡肽水溶液在不同温度 [2] 下的近红外光谱, 经连续小波变换提高光谱分辨率后, 利用独立成分分析提取具有独立变化规律的光谱信 [3] 息 提取出三个与水分子结构相关的独立成分, 分别包含了溶液中自由水分子 (S0) 以及含有一 (S) 二个氢键 (S2) 的水分子的光谱信息 基于温度变化的结果表明溶液中的水合作用确实存在, 并且 D5 与水之间的水合作用在一定程度上提高了 D5 周围水化层中氢键网络的热稳定性 基于浓度变化的结果显示第一水化层中的每个水分子通过一个氢键与 D5 相结合 此外, 不同温度下 S 峰强度随浓度的变化可以用来指示 D5 结构变化过程中水合作用的变化 这种变化可能是由于在 55-60 温度范围内两种不同形式的转角结构发生互换导致 关键词 : 温控近红外光谱 ; 独立成分分析 ; 水合作用 ; 寡肽 ; 水分子参考文献 [] Tsenkova, R. NIR News. 2006, 7(4): 0. [2] Shao, X.G.; Leung, A.K.; Chau, F.T. Accounts Chem Res. 2003, 36(4): 276. [3] Hyvärinen, A.; Oja, E. Neural Networks. 2000, 3(4 5): 4. 国家自然科学基金项目 (No. 275074) 资助 77

O-2-7 利用大规模 ReaxFF MD 初步探索孔道对煤热解过程的影响 郑默,*, 李晓霞,2,*, 郭力,2 中国科学院过程工程研究所多相复杂系统国家重点实验室, 北京 0090 2 中国科学院大学化学化工学院, 北京,00049 *Email: mzheng@ipe.ac.cn, xxia@ipe.ac.cn 深入了解煤热解反应机理对实现煤的高效和清洁利用至关重要 影响煤热解化学反应的主要影响因素包括温度 颗粒内的孔道 煤颗粒表面结构 反应气氛 升温速率等等 其中, 煤结构中的微孔道 (0.4-.2 nm) 对煤分子及其热解产物, 特别是焦油产物的生成至关重要 由于煤结构本身的复杂和不均一性, 并且热解为高温自由基过程, 对煤热解自由基和中间产物的演化仍缺乏原位测定技术 这几年, 化学反应分子动力学 ReaxFF MD 被广泛应用于热解 爆炸 金属催化和新材料设计中, 为从分子角度探索孔道对煤热解反应过程的影响提供了新的视角 本文首先基于原煤的实验测定数据 ( 元素和工业分析,2 个核磁共振数据 ), 构建了两个所含原子数相同 (99,544 个原子, 国际上目前为止模拟的最大煤模型 ) 组成相同, 但具有不一样孔道分布的大规模海拉尔褐煤模型, 其中一个为密实体系, 另一个则人为地添加了 0 Å 的孔道 采用 GPU 高性能计算的 GMD-Reax, 对两个褐煤模型在相同条件下分别进行 ReaxFF MD 模拟, 并利用基于化学信息学的 VARxMD 对模拟结果的产物和化学反应进行分析, 初步探索了煤孔道对煤热解的影响 模拟结果得到了海拉尔褐煤的主要热解产物 ( 焦炭 焦油和气体 ) 的生成趋势 (Fig. ) 主要小分子气体的演化 桥键的裂解行为 自由基的生成和消耗规律等在两个模型热解过程中的相似与不同 ; 并表明孔道会促进煤结构中 C-C 键的断裂, 有利于轻质焦油 (C5-C3 物质 ) 的生成 Fig. Pore effects on the weight percentage evolution of major pyrolyzates with temperature for Hailaer brown coal pyrolysis obtained from the heat-up ReaxFF MD simulation with a relatively slow heating-rate of 2 K/ps 关键词 :ReaxFF MD; 大规模模拟 ; 煤热解 ; 孔道的影响参考文献 [] Zheng, M.; Li, X.; Nie, F.; Guo, L. Energy & Fuels 207, 3 (4): 3675-3683. [2] Li, X.; Mo, Z.; Liu, J.; Guo, L. Molecular Simulation 205, 4 (-3): 3-27 78

O-2-8 并行科技, 助力高效提升化学计算应用在超算上的性能 李伯杨 北京并行科技有限公司 79

O-2-9 基于代谢组学数据特征的稳健的变量选择方法研究 易伦朝,* 付光辉 2 昆明理工大学食品安全研究院, 昆明,650500 2 昆明理工大学理学院, 昆明,650500 *Email: yilunzhao@kmust.edu.cn 代谢组学数据具有维度高 干扰变量多 类不平衡等特点 偏最小二乘 - 判别分析法 (Partial least squaresdiscriminant analysis, PLS-DA) 是目前在代谢组学研究中应用最为广泛的一种分类方法 许多的变量选择方法也是基于该算法提出的 然而, 由于 PLS-DA 具有过拟合数据的风险, 且在无信息变量和干扰变量等的影响下, 该方法筛选出的生物标记物往往不够稳定 本研究提出了一种稳健的变量选择算法,SRS-SVM (sparse regularization variable selection with subsampling-linear support vector machine) 算法 该方法利用重复采样技术建立一系列的子模型, 将基于稀疏正则化的变量选择方法, 如 LASSO 和稀疏偏最小二乘法, 与支持向量机相结合, 在一个优化了的变量空间去获得最优的变量组合和最优的分类精度 内部检验和外部检验的结果均表明, 在预测精度和筛选变量的稳定性等方面,SRS-SVM 算法均优于 PLS-DA 方法 该算法应用于冠心病和颅脑损伤这两个不同的代谢组学数据集中, 其筛选的潜在生物标记物的分类精度均优于基于 PLS-DA 的载荷矩阵 (Loading) 法, 回归系数法 (Regression coefficients) 和变量重要性投影法 (Variable Importance in Projection,VIP) Fig. The flowchart of subsample-based stable sparse biomarker screening and classification algorithm 关键词 : 变量选择 ; 代谢组学 ; 稀疏正则化参考文献 [] Fu, G.; Zhang, B.; Kou, H.; Yi, L. Chemometrics and Intelligent Laboratory Systems, 207, 60: 22. [2] Yun, Y.; Liang, F.; Deng, B.; Lai, G.; et al.. Metabolomics, 205, (6): 80

O-2-20 Fast Pure Ion Chromatograms Extraction Method for LC-MS Zhimin Zhang, Wang Rong, Hongcao Ji, Hongmei Lu College of Chemistry and Chemical Engineering, Central South University, Changsha, 40083 *Email: zmzhang@csu.edu.cn Liquid chromatography coupled with mass spectrometry (LC-MS) has shown great potential in analysis complex samples. However, informative feature detection is still challenge since the electrospray ionization in LC-MS tends to produce ninety percent or more ions not originated from compounds of interest. The concept of pure ion chromatogram (PIC) is effective to extract informative ions, but tradition PIC methods are time-consuming because of their theories and programming languages. In this study, we present a novel method, called Fast Pure Ions Chromatograms (FPIC), for extracting PICs from raw LC-MS dataset effectively and quickly. This method can search ion of PIC from its maximum bi-directionally and adaptively, which can improve the stability and reduce the computation time drastically. A further speedup has been achieved by exploiting multi-core computing, advanced vector extensions (AVX) instruction and C++ programming language. FPIC was validated by analyzing two LC-MS datasets: MM4 and MM48 datasets. Results show that FPIC outperformed traditional methods in the recall rate. Furthermore, the method is very fast with few adjustable parameters, which leads to an approximately 00-fold speedup over traditional PIC methods. An open source implementation of the FPIC method is available at the package PyMass (https://github.com/zmzhang/pymass). Fig. Schema of pure ion chromatogram extraction with FPIC method. The red triangle is seed of this PIC. The two red horizon lines are upper and lower m/z tolerances, and m/z tolerance can be estimated from standard deviations of m/z values of GNN ions. FPIC starts from seed and searches for ions bi-directionally. The searching procedure stops when meets ion beyond the m/z tolerance. The blue profile is the extracted PIC by FPIC method. Keywords: Pure Ion Chromatogram; LC-MS; Feature Detection References: [] Ji, H., Lu, H., Zhang, Z. RSC Advances, 206, 6: 56977. [2] Ji, H., Zeng, F., Xu, Y., Lu, H., Zhang, Z. Anal. Chem., 207, 4:763. 8

O-2-2 多元曲线分辨旋转模糊评估和应对策略 张欣, 张卓勇 * 首都师范大学化学系, 北京市海淀区西三环北路 05 号,00048 *Email: gusto2008@vip.sina.com 多元曲线分辨 (Multivariate Curve Resolution,MCR) 在二线性数据解析中发挥了重要作用, 能够提取来自光谱 质谱 色谱等不同方法测定的复杂体系中纯组分的特征信号及其对应浓度, 应用范围涵盖了生物 食品 药品 农业 环境等领域, 伴随着新的约束方法的开发和应用, 多元曲线分辨有望在这些领域中解决更多实际应用问题 [] 在当下热门的组学( 基因组学 蛋白质组学 代谢组学 脂质组学 ) 和高光谱成像研究中 [2], 多元曲线分辨以其灵活性和易用性, 更重要的是解析信号理化意义的可解释性, 焕发出新的生命力 然而长期以来与类似化学计量学方法对比, 多元曲线分辨的应用中受到同行讨论最多的就是结果的非唯一性问题 二线性分析分辨方法往往存在旋转模糊, 导致可行解是一个范围, 而且在约束不充分的情况下难以决定真实解的具体位置 为此 MCR 研究的研究人员开发出一系列的评估旋转模糊范围的方法, 例如 Borgene-Rajko[3] 单纯形 多边形膨胀[4] MCR-BANDS 等方法, 在此我们将对不同方法进行比较 为了解决旋转模糊的问题, 在 MCR 约束中也可以采取诸多策略, 根据现有测试方法和样品的性质以及对数据的深入了解, 可以采用不同约束的方法降低甚至消除扭曲模糊带来的影响 本文分别对拉曼光谱成像测定组织 近红外光谱测定酶促反应的数据分别施加了选择性约束和三线性约束, 使得最终分析结果不会受到扭曲模糊的影响, 并获得了具有丰富理化信息的纯组分信号, 能够极为方便地解释在组织结构和反应过程中发生的物质成分和结构的变化 关键词 :MCR; 旋转模糊 ; 化学计量学 ; 约束 ; 光谱 参考文献 [] Tauler, R., Chemom. Intell. Lab. Syst. 995, 30: 33 46. [2] Zhang, X., Juan, A., and Tauler, R., Appl. Spectrosc., 205, 69: 993 003. [3] Róbert, R. and Krisztina, I., J. Chemom. 200, 9: 448 463. [4] Sawall, M. and Neymeyr, K., Anal. Chim. Acta, 204, 828: 7 26. * 国家重大学科仪器开发专项 (202YQ40005) 国家自然科学基金 (22750) 和北京市科技创新平台项目 (75303900) 资助 82

O-2-22 基于遗传算法优化的约束背景双线性分解算法用于改进 高效液相色谱灰色分析体系的校正结果张雅雄, 聂先玲 2 *, 张雅雄 山西师范大学化学与材料科学学院, 山西省临汾市尧都区贡院路 号,04004 2 山西师范大学磁性分子与磁性信息材料教育部重点实验室, 山西省临汾市尧都区贡院路 号,04004 *Email: zhangyx@sxnu.edu.cn 该研究工作采用约束背景双线性分解算法对以高效液相色谱方法分离分析的灰色分析体系进行了多元校正研究 针对采用包括约束背景双线性分解算法在内的矩阵校正方法处理高效液相色谱灰色分析体系的固有缺陷, 即在相关组分的色谱保留时间重现性较低的情形下多元校正的结果不理想, 对约束背景双线性分解算法进行了改进, 即将待测组分的浓度与组分的色谱保留时间同时作为优化的参量引入约束背景双线性分解算法, 并采用遗传算法优化约束背景双线性分解算法, 对于模拟的组分保留时间飘移严重的高效液相灰色分析体系及保留时间重现性不佳的多种酚类化合物组成的实际高效液相色谱灰色分析体系进行了多元校正分析, 成功克服了经典约束背景双线性分解算法的固有缺陷, 取得了较理想的多元校正结果 另外, 该研究所建议的方法的校正结果也显著优于传统的残差双线性分解法以及秩消失因子分析法 关键词 : 约束背景双线性分解算法 ; 遗传算法 ; 高效液相色谱灰色分析体系 ; 改进多元校正方法参考文献 [] Liang, Y. Z.; Manne, R.; Kvalheim, O. M. Chemom. Intell. Lab. Syst., 992, 4(/3): 75. [2] 陈文灿, 崔卉, 陈增萍, 许静. 化学学报, 997, 55(7): 693. 83

O-3-0 纳米粒子单接枝均聚物链体系的分相及桥连行为 张添财, 付超, 杨颖梓 *, 邱枫 复旦大学, 高分子科学系, 聚合物分子工程国家重点实验室, 上海市邯郸路 220 号,200433 *Email: yang_yingzi@fudan.edu.cn 纳米粒子具有良好的电学和力学性能等, 而高分子聚合物可形成多种有序的微相结构, 可诱导纳米粒子有序排列 在每个纳米刚球粒子上单点接枝一根均聚物链, 形成蝌蚪形和流星锤形的大分子, 且聚合物链与 [] 纳米粒子化学不相容时, 可微相分离形成多种有序结构 我们使用自洽场理论结合密度泛函理论的方法, 研究了蝌蚪形大分子与流星锤形大分子的微相分离行为, 并给出相图 蝌蚪形大分子和对称的流星锤形大分子可形成层状相 柱状相 球状相和 Gyroid 相等分相结构, 与线性两嵌段和三嵌段高分子相似, 然而结构的特征长度更小, 且相图极不对称 材料中高分子链的桥连结构可改善材料的韧性 在传统的线性嵌段聚合物体系中, 可通过增加嵌段数目增 [2] 强链的桥连比例 在纳米粒子单接枝高分子链体系中, 相结构的周期非常小, 且纳米粒子球相区具有较大空隙允许聚合链穿过 聚合物链为屏蔽球之间的刚性体积排除, 穿过纳米球相区, 升高了球 / 链相区的界面能, 但同时也获得更大的构象熵 对称的流星锤形分子本体层状相时, 均聚物链可跨跃五个周期, 与近邻的十个周期 ( 每侧五个 ) 通过桥连而连接, 如图 所示 我们将流星锤形大分子在层状相里的桥连行为与等分子体积的 ABA 线型三嵌段高分子比较, 并关注纳米粒子与共聚物的不相容性 均聚物的长度 分子的不对称性等对层状结构的桥连性质的影响 我们的工作为设计具有 0 纳米以下尺度的规整结构的材料提供了理论指导 Fig. Bridging and looping fraction of the symmetric bola-form molecules in lamellae structure. The volume fraction of the nanoparticles is 0.5. The insert shows the bridging and looping fraction of ABA block copolymer with the same parameters. 关键词 : 纳米粒子 ; 巨型表面活性剂 ; 相分离 ; 桥连参考文献 [] Lee, J. Y.; Balazs, A. C.; Thompson, R. B.; Hill, R. M. Macromolecules 2004, 37: 3536. [2] Klymko, T.; Markov, V.; Subbotin, A.; ten Brinke, G. Soft Matter 2009, 5: 98. 84

O-3-02 聚合物共混理论 : 单链构象及 点 徐玉赐,Zhen-Gang Wang 2 宁波大学材料科学与化学工程学院, 浙江宁波,352 2 Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA, USA, 925 *Email: xuyuci@nbu.edu.cn 理想链模型是高分子物理中非常重要的模型, 因为它考虑了高分子最重要的性质 链的连接性, 另外一方面, 聚合物在稀溶液 ( 包括小分子溶剂及高分子溶剂 ) 中, 当处于 温度的时候, 聚合物表现出理想链的行为 根据 点的定义 : 此时链长无限长, 溶液无限稀, 并且两体相互作用和三体相互作用抵消 当链长无限长的时候, 对于小分子溶剂, 相分离的临界点 Coil-to-Globule 转变点以及 点都是 =0.5. 在有限链长情况下, 我们可以通过计算其 Coil-to-Globule 转变点, 来定义 区域 之前研究发现 区域宽度随着分子链长的增加而以 N -/2 关系逐渐的减小, 外推到 N 为无限长的时候, 即可以得到 点 但是对于聚合物共混体系, 当 N( 溶质链长 )=N( 溶剂链长 ) 时候, 临界点是 N=2.0, 点为 N=0.5, 这也就说明增加 N 的时候, 体系会先经历 Coil-to-Globule 的转变, 然后才发生相分离 为了理解这个问题, 我们需要研究在共混时的 点, 而根据的 点的定义, 我们讨论两种情况, 一是保持溶剂链长不变, 然后一直增加溶液链长, 另外一种情况就是保持溶剂链长与溶液链长的比例, 然后增加链长 对于第一种情况, 我们发现当溶质链长大于溶剂链长的 N 2 时候 (N >N 2 ), 共混物体系表现出于小分子溶液类似的性质, 点为 N=0.5. 而且 区域也以 N -/2 关系衰减 对于第二种情况, 我们发现 点 N 仍然是 0.5, 但是 区域宽度却以 N -2/3 趋势衰减 关键词 : 聚合物共混 ; 点 ;Coil-to-Globule 转变 ( 五号宋体, 关键词个数不超过 5 个 ) 参考文献 [] Wang, R.; Wang, Z. G. Macromolecules 204, 47: 4094. [2] Wang, R.; Wang, Z. G. Macromolecules 202, 45: 6266. 85

O-3-03 嵌段共聚物诱导纳米粒子组装成纳米线 纳米环和纳米簇 马世营 2, 汪蓉,* 南京大学化学化工学院高分子科学与工程系配位化学国家重点实验室, 江苏南京,20023 2 泰山学院化学化工学院, 山东泰安,27000 *Email: wangrong@nju.edu.cn 纳米粒子和嵌段共聚物的杂化聚集体不但具有各个组分固有的性质, 而且能够产生新的特殊的性质, 可以应用于医药领域 生物科学 电子学 催化等领域 纳米粒子在嵌段共聚物组装体中的位置 分布方式等聚集行为对杂化聚集体的应用产生重要的影响 本文利用耗散粒子动力学方法研究了嵌段共聚物接枝纳米粒子在溶液中的自组装行为, 重点研究了纳米粒子在不同形态的组装体中的聚集行为 模拟研究发现通过改变纳米粒子表面的接枝数量和疏水链段的长度, 嵌段共聚物能够自组装形成形态丰富的聚集体, 包括球形 蠕虫状 盘状 环状胶束以及囊泡 ; 重要的是纳米粒子可以在胶束中聚集形成纳米线 纳米环以及纳米簇 另外, 通过改变纳米粒子和疏水链段之间的相互作用力, 可以控制纳米粒子在胶束的聚集行为 随着相互作用力的增大, 纳米粒子在胶束中逐渐由均匀分布方式过渡到几个纳米粒子聚集的形式, 形成纳米粒子簇的聚集方式 关键词 : 嵌段共聚物纳米粒子自组装耗散粒子动力学参考文献 [] Liu, Y.; Li, Y.; He, J.; Duelge, K. J.; Lu, Z.; Nie, Z. J. Am. Chem. Soc. 204, 36: 2602. [2] Cheng, L.; Wang, C.; Feng, L.; Yang, K.; Liu, Z. Chem. Rev. 204, 4: 0869. [3] Ma, S.; Hu, Y.; Wang, R. Macromolecules 205, 48: 32. [4] He, J.; Liu, Y.; Babu, T.; Wei, Z.; Nie, Z. J. Am. Chem. Soc. 202, 34: 342. 86

O-3-04 半刚性高分子体系粘度行为 徐晓雷, 陈继忠 *, 安立佳 中国科学院长春应用化学研究所, 高分子物理与化学国家重点实验室, 长春市人民大街 5625 号, 邮编 :30022 *Email: jzchen@ciac.ac.cn 高分子流体区别于小分子流体的一个显著特征就是其在剪切场下的粘度行为 通常情况下, 其粘度在弱剪切条件下为常数, 而在强剪切条件下则随剪切变强而减小, 即著名的剪切变稀效应 [-2] 需要注意的是, 剪切变稀多见于柔性高分子体系, 但是并不能描述所有高分子的粘度行为, 比如对于具有链刚性的液晶体系, 其粘度常表现出怪异的三段剪切, 即剪切变稀 - 平台 - 剪切变稀, 而且关于三段剪切的微观机理目前也未有令人信服的解释 再者, 在从柔性链过渡到刚性链的过程中间, 高分子体系会展现出怎样的粘度行为这一问题目前也没有明确的答案 [3] 因此, 我们针对不同刚性的线形链开展了其粘度行为的相关研究 在本工作中我们采用非平衡态分子动力学模拟 (NEMD) 方法研究了不同刚性线形链体系在剪切场下的粘度行为 模拟结果重复了实验上观测到的多种粘度曲线样式 进一步的结构分析表明上述不同的粘度曲线背后所蕴含的微观机理可以分为两类 : 对于刚性较小的体系, 粘度行为与分子链本身的构象变化有关 ; 对于刚性较大的体系, 粘度行为与局域的结构性质有关 特别的, 对于链持续长度接近轮廓长度的体系, 首次发现了四段剪切行为的存在, 并给出了上述行为的微观结构起源 这些研究结果详细阐述了宏观粘度的微观结构机理, 加深了对高分子体系的认识水平 关键词 : 高分子 ; 半刚性 ; 粘度 ; 微观机理参考文献 [2] M. Doi and S. F. Edwards, The Theory of Polymer Dynamics, Clarendon Press, New York, 986. [3] M. Rubinstein and R. H. Colby, Polymer Physics, Oxford University Press, New York, 998. [4] R. G. Larson, The Structure and Rheology of Complex Fluids, Oxford University Press, New York, 999. 87

O-3-05 Theoretical Investigation of the Mechanism of Photochemical Ligand Ejection in Transition Metal Complex Fu-Quan Bai International Joint Research Laboratory of Nano-Micro Architecture Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 30023, People s-republic of China. *E-mail: baifq@jlu.edu.cn Keywords: Second- and third-row transition-metal elements (e.g. Re, Ru, Os, and Ir) have attracted enormous interest due to their attractive photo-physical properties that make them potentially amenable to application in light-emitting technologies, dye-sensitized photovoltaics, phosphorescent biological imaging microscopy and solar catalysis. The utility in phosphorescent and electron/energy-transfer applications stems from the relatively long-lived triplet metal-to-ligand charge-transfer ( 3 MLCT) states that complexes of these metals exhibit. These can however be deactivated by triplet metal-centered ( 3 MC) states if these are sufficiently close in energy to photoexcited 3 MLCT states and can induce photochemical reactivity such as ligand-loss or isomerization. For example, photochemical reactivity can be designed into ruthenium(ii) complexes; inclusion of steric bulk in the ligand set in order to weaken metal ligand bonds lowers the 3 MC state making thermal population from 3 MLCT states after photoexcitation achievable. 88

O-3-06 分子动力学模拟与模型结合研究填料 ( 石墨烯, 碳纳米管 ) 接枝分子链对尼龙纳米复合材料导热性能的影响 * 2 高洋洋,Florian Muller-Plathe 先进弹性体研究中心, 北京化工大学, 北京,00029 2 Eduard-Zintl-Institut für Anorganische und Physikalische Chemie and Profile Area Thermofluids & Interfaces, Technische Universität Darmstadt, Alarich-Weiss-Str.8, 64287 Darmstadt, Germany *Email: gaoyy@mail.buct.edu.cn 通过使用反转非平衡分子动力学模拟方法, 我们使用全原子模型考察了石墨烯碳纳米管接枝分子链对尼龙纳米复合材料导热性能的影响 石墨烯尼龙界面热导与接枝分子链密度成正比 ; 但是随着接枝长度的上升, 它先上升然后逐渐趋于饱和 但是由于接枝分子链显著地破坏了石墨烯的平面共轭结构, 石墨烯本身的热导显著下降 我们用经验方程描绘了材料界面热导与接枝密度和接枝长度的关系 通过结合 EMA 模型, 我们发现石墨烯尼龙纳米复合材料热导在中等接枝条件下达到最大值 我们的模拟结论能与实验基本符合 另外, 我们考察了碳纳米管间热导与接枝密度, 接枝长度和管间距离的关系 我们提出了一个热环流模型描述了三者之间的关系 本工作有助于提高对接枝法改善聚合物填料复合材料热导的认识, 为制备高热导率的聚合物复合材料提供新的思路 关键词 : 分子动力学模拟 ; 尼龙复合材料 ; 接枝 ; 导热 参考文献 [] Yangyang Gao, Florian Müller-Plathe. Journal of Physical Chemistry B. 206, 20, 336-346. 89

O-3-07 Molecular conformation study of gellan polysaccharide in crystal and solution states Liang LI, Yan XIANG 2, Huai SUN,* School of chemistry and chemical engineering,shanghai Jiao Tong University,800 Dong Chuan Rd,200240 *Email: huaisun@sjtu.edu.cn Gellan gum is an innovated polysaccharide molecule of non-toxic, microbial, heat and acid resistance gelling material interested by many industries including food, pharmaceuticals, and chemical engineering sectors. The flexible polysaccharide backbone and large degree of freedom of gellan present a great challenge in aspects of properties design of relevant products due to the unclear molecular conformation. We report here a study of gellan molecular conformation in both crystal and solvated states via molecular simulation methods. Firstly, we have validated an all-atom force field [] by crystal and quantum mechanics data. In crystal state, the gellan molecules have formed a parallel, half-staggered, double helix (DH) molecular conformation [2]. We showed that the energy interaction between DH is much stronger than that between the two single chains inside a DH, and revealed the location of water and ions in the crystal. Secondly, the solvation mechanism of crystal in water has been studied with Umbrella Sampling method, the free energy calculations of DH bundles disruption and a double helix unwinding into two single random coiled chains are presented and compared. Finally, the molecular conformation of double-helix and single chain gellan were studied at both low and high concentration with Meta-Dynamics method, where the persistence length, end-to-end distance and radius of gyration were used as collective variables. Fig. Truncated view of a Gellan Crystal. Fig. 2 Glycosidic linkage validation. Fig. 3 Free energy of a single chain in solution Red lines: DH gellan; Green dots: Water. with end-to-end distance reaction coordinates. Keywords: Gellan; Molecular Simulation; Free Energy; Double-Helix; References: [] Guvench, O., E. Hatcher, R. M. Venable, R. W. Pastor and A. D. MacKerell Jr. Journal of chemical theory and computation. 2009, 5(9): 2353-2370 [2] Chandrasekaran, R., R. P. Millane, S. Arnott and E. D. Atkins. Carbohydrate Research. 998, 75(): -5. 90

O-4-0 Ab Initio Molecular Dynamics Simulations of Nickel-Catalyzed Transformation of Amorphous Carbon into Graphene in Rapid Thermal Processing Shuang Chen,* Kuang Yaming Honors School, Nanjing University, Nanjing, Jiangsu 20023, China *Email: chenshuang@nju.edu.cn Ab initio molecular dynamics (AIMD) simulations are employed to demonstrate atomic-scale mechanism of the Ni-catalyzed transformation of amorphous carbon (a-c) into graphene in experimental rapid thermal processing, where graphene was directly grown on various dielectric surfaces via the evaporation of surplus Ni and C at 00 C. We found that the a-c-to-graphene transformation follows the metal-induced crystallization and layer exchange mechanism, rather than the well-established dissolution/precipitation mechanism typically involved in Ni-catalyzed chemical vapor deposition growth of graphene. Our AIMD simulations suggest that the easy evaporation of surplus Ni with excess C is likely attributed to the formation of a viscous-liquid-like Ni C solution within the temperature range of 900 800 K and to the faster diffusion of C atoms than that of Ni atoms above 600 K. Because the temperature increasing rate is considerably faster in our AIMD simulations than in realistic experiments, defects in the grown graphitic C structures are kinetically trapped. Fig. Snapshot of defective graphitic C layer on Ni 3C layer at 200 K and variations of mean square displacement with time of Ni (solid lines) and C (dashed lines) atoms in the Ni 3C layer based on our AIMD simulations. The corresponding linear fitting of the MSD time curves is in blue to estimate self-diffusion coefficients, D, of Ni and C atoms. Keywords: ab initio molecular dynamics simulations; Ni-catalyzed graphene growth; rapid thermal processing References: [] Chen, S.; Xiong, W.; Zhou, Y. S.; Lu, Y. F.; Zeng, X. C. Nanoscale 206, 8: 9746. 9

O-4-02 The combination of superhalogens and Brønsted acids HX (X=F, Cl, Br): An effective strategy for designing strong superacids Fu-Qiang Zhou and Bing Yin* College of Chemistry and Materials Science, Northwest University, Xi an, 7027 *Email: rayinyin@nwu.edu.cn A series of 27 composite structures, consisting of superhalogen and Brønsted acid, is designed and systematically studied based on combined ab initio and DFT calculations focusing on their potentials as novel superacids. As indicated by high-level CCSD(T) results, all the composites here fulfill the theoretical criterion of superacid and the acidities of two of them are close to the strongest superacid ever reported. The influences of various factors on the superacid properties of these composites were analyzed in detail. Our results demonstrate that the acidity of these superacids is mainly determined by the superhalogen components while the effect of Brønsted acids, irrespective of their number or type, is relatively mild. Therefore, it is probable to design novel composite superacid with enhanced property through the regulation of the superhalogen component. It is encouraging that MP2 and DFT could also provide reliable results when compared with high-level CCSD(T) method. The reliability of these low-cost methods implies the capability of theoretical calculations for future composite superacid of enlarged size and thus it is highly probable that effective guide to the related experimental research could be provided by the theory. Fig. Superacid based on combination of superhalogen and HF (X=F, Cl, Br) Keywords: Superacid; superhalogen; CCSD(T); DFT References: [] Zhou, F-Q.; Yin, B.; and et al. Inorg. Chem. 207, accepted for publication. 92

O-4-03 Water Assistant Hydrogen Evolution Reaction (HER) Catalyzed by Molecular [MoS2] 2+ Tilong Yang and Li Dang* Department of Chemistry and Key Laboratory for Preparation and Application of Ordered Structural Materials of Guangdong Province, Shantou University, Guangdong 55063, P. R. China ldang@stu.edu.cn Long and Chang et al. [] synthesized a molecular complex [MoS2] 2+ ([(PY5Me2)MoS2] 2+, PY5Me2 = 2,6-bis(,-bis(2-pyridyl)ethyl)pyridine) that mimics the reactive edge sites of the nanoparticulate MoS2 for the electrocatalyzed hydrogen evolution reaction (HER) at room temperature. Here, we present a study of the mechanism of [MoS2] 2+ catalyzed HER by using DFT calculation. The reduction of the side-on bound 3 [MoS2] 2+ gives the end-on configuration 4 [MoS-S] +, accompanying with the cleavage of the one Mo-S bond. Then the protonation of the undercoordinated sulfur occurs. The second reduction step changes the protonated 4 [MoS-SH] 2+ to 3 [MoS-SH] +. AIM charge analysis shows that 3 [MoS-SH] + presents a sulfur-hydride character. Water assisted HER from 3 [MoS-SH] + and hydrated proton is the most favorable pathway. Other HER pathways cannot compete with Water assisted HER from 3 [MoS-SH] + and hydrated proton due to high activation barriers. Keywords Hydrogen Evolution Reaction, MoS2, DFT Fig. Possible pathways for H2 generation by the active 3 [MoS-SH] + (PY5Me2 was eliminated for clear presentation). References Karunadasa, H. I.; Montalvo, E.; Sun, Y.; Majda, M.; Long, J. R.; Chang, C. J. Science, 202, 335, 698. 93

O-4-04 Quintuple super bonding between superatoms of metallic clusters Longjiu Cheng (程龙玖) 安徽大学化学化工学院 合肥 安徽 23060 *Email: clj@ustc.edu Jellium model is widely used in studies of metallic clusters. In this model, the valence electrons of a cluster are delocalized in the cluster volume and fill discrete energy levels. Based on the jellium model, atomic assemblings with magic number electrons can act as superatoms, and such a superatom concept has achieved great success in explaining the stability of pure metal clusters. In our previous studies, we propose a concept for bonding between superatoms super valence bond (SVB), of which superatoms can share both valence pairs and nuclei for shell closure thus forming delocalized super bonding. This concept shows new insights in understanding the stability of ligand protected gold clusters.2-4 Looking back to the pioneering mass experiments of sodium clusters at 984, we found some new stories about the magic numbers 26e and 30e that dissatisfy the rule in Jellium model. It is also verified that the 26e Li20Mg3 cluster has a perfect D3h double-icosahedral global minimum structure with a large HOMO-LUMO energy gap (.44 ev). From the molecular orbital diagrams and chemical bonding patterns, it is found that each icosahedron in Li20Mg3 cluster is an independent superatom and a molecule-like electronic shell-closure is achieved via quintuple bonding between two superatoms: [8e](D2S)5 (D2S)5[8e]. Similar quintuple bonding also exists in the 30e double-icosahedral Li8Mg3Al2 cluster: [8e](D2S)7 (D2S)7[8e]. Analogies of quintuple super bonding in the 26e/30e clusters and quintuple bonding in V2/Re2 molecules are very beautiful and straightforward (see Figure). References:. L. Cheng*, J. Yang*, "Communication: New Insight into Electronic Shells of Metal Clusters: Analogues of Simple Molecules." J. Chem. Phys. 203, 38, 40. 2. L. Cheng*, C. Ren, X. Zhang, J. Yang*, "New insight into electronic shell of Au38(SR)24: a superatomic molecule." Nanoscale 203, 5, 475-478. 3. Y. Yuan, L. Cheng*, J. Yang*, "Electronic Stability of Phosphine-Protected Au20 Nanocluster: Superatomic Bonding." J. Phys. Chem. C 203, 7, 3276-3282. 4. L. Cheng*, X. Zhang, B. Jin, J. Yang* "Superatom atom super-bonding in metallic clusters: a new look to the mystery of an Au20 pyramid", Nanoscale 204, 6, 2440. 94

O-4-05 Coarse-grained simulations of peptide aggregation by nanoparticle Bin Li, Xinghua Shi,* CAS Key Laboratory for Nanosystem and Hierarchy Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing 0090, China *Email: shixh@nanoctr.cn Protein aggregation could lead to amyloid formation, which is the source of some human diseases, like Alzheimer's disease, Parkinson's disease and so on []. Nanoparticle could enhance the aggregation of peptides by adsorbing them on nanoparticle surface. Here we study the peptide aggregation on nanoparticle surface via coarse-grained Monte Carlo simulations. The peptide was represented by a linear chain model [2], and the spherical nanoparticle was constructed by using a couple of small coarse-grained beads. We found that the β-sheet structure can form on the nanoparticle surface, and the aggregate size on the surface is larger than other aggregates in the solution. In addition, the formation of peptide fibrillation also depends on the nanoparticle size, in other words, the curvature of nanoparticle. The aggregates form more easily as the nanoparticle is larger, or the curvature is smaller. To investigate the influence from the curvature effect, we also calculated the bending energy of β-sheet, as well as the adsorption energy from nanoparticle. The ratio between them is smaller as the curvature decreases, which means that the adsorption energy dominates the system when nanoparticle size is larger. Keywords: peptide, nanoparticle, aggregation, Monte Carlo simulation References: [] Linse, S.; Cabaleiro-Lago, C.; Xue, W.-F.; Lynch, I.; Lindman, S.; Thulin, E.; Radford, S. E.; Dawson, K. A. PNAS 2007, 04: 869. [2] Zhang, R.; Duan, X.; Shi, T.; Li, H.; An, L.; Huang, Q. Macromolecules 202, 45: 620. 95

O-4-06 Layer-Dependent Electronic Properties of Phosphorene-like Materials and Phosphorene-Based van der Walls Heterostructures Y. C. Huang*, X. Chen, C. Wang Center for Nano Science and Technology, College of Chemistry and Material Science, The Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui Laboratory of Molecule-Based Materials, Anhui Normal University, Wuhu, 24000, Peoples Republic of China *Email: huangyc@mail.ahnu.edu.cn Black phosphorus is a layered semiconducting allotrope of phosphorus with high carrier mobility. Its monolayer form, phosphorene, is an extremely fashionable two-dimensional material which has a promising potential in transistors, optoelectronics and electronics. However, phosphorene-like analogues especially phosphorene-based heterostructures and their layer-controlled electronic properties are rarely systematically investigated. In this work, the layer-dependent structural and electronic properties of phosphorene-like materials, i.e., mono- and few-layer MXs (M=Sn, Ge; X= S, Se), were first studied via first-principles calculations, and then the band edge position of these MXs as well as mono- and few-layer phosphorene were aligned. It was revealed that van der Walls heterostructures with Moiré superstructure formed by mutual coupling among MXs and among MXs and few-layer phosphorene is able to show a type-i or type-Ⅱ characteristic and I-Ⅱ or Ⅱ-I transition can be induced by adjusting the number of layer. Our work is expected to yield a new family of phosphorene-based semiconductor heterostructures having tunable electronic properties through altering the layer number of the composite. Fig. A new family of phosphorene-based semiconductor van der Waals heterostructures with layer-dependent electronic properties was yielded by first-principles calculations. Keywords: density functional theory; van der Walls heterostructure; type-Ⅱ alignment; phosphorene; electronic property References: [] Huang, Y.; Chen, X.; Wang, C.; Peng, L.; Qian. Q.; Wang. S. Nanoscale. 207, 9: 866. 96

O-4-07 Structures and Properties of the Ultra-small TiO2 and ZnO Nanoparticles,* 陈名扬, David A. Dixon 2 北京计算科学研究中心, 北京市海淀区西北旺东路 0 号院中关村软件园二期东区 9 号楼,0093 The University of Alabama,Tuscaloosa,AL 35487, USA *Email: mychen@csrc.ac.cn Global minimum energy structures for (TiO2)n, n 384 [], and (ZnO)n, n 68 [2], were determined theoretically by using a novel bottom-up evolutionary algorithm followed by a local geometry optimization at the density functional theory level. The magic -D, 2-D and 3-D ultra-small nanoparticles (USNPs) are found to be tubular, tube array-like, and anatase-like. The magic (ZnO)n particles are mostly single-, double- and triple-layered octahedral cages. (ZnO)32 and (ZnO)68 are triple-layer cages with a diameter 2 nm in each dimension. Surface energy densities were predicted for surface fragments at the different position of the (TiO2)n USNPs using a fragment-based energy-partition model that we developed to relate the energy with geometry for USNPs with local translational symmetries. The normalized clustering energies at the thermodynamic limit and the ideal aspect ratios were predicted for the 2-D and 3-D (TiO2)n USNPs using the fragment-based model. The adiabatic growth pathways were proposed for (TiO2)n, and (ZnO)n USNPs. Molecular orbital and density of states analysis shows the quantum confinement effects on band gaps of the (TiO2)n, and (ZnO)n USNPs differ from the effects predicted using the effective mass approximation. This is likely due to the different localities of the molecular orbitals near the valence band maximum and conduction band minimum. The possible catalytically active sites of the (TiO2)n were suggested based on the property analysis. Fig. Normalized clustering energy as a function of n -/3 for (TiO 2) n USNPs. 关键词 :TiO2;ZnO;clusters; USNP; surface energy density 参考文献 [] Chen, M.; Dixon, D. A. Nanoscale, 207, 9: 743-762. [2] Chen, M.; Straatsma, T. P.; Fang, Z.; Dixon, A. Dixon. J. Phys. Chem. C, 206, 20: 20400-2048. 97

O-4-08 Enhancing the Oxidation of Toluene with External Electric Fields: a Reactive Molecular Dynamics Study Yi He,*, Shen Tan, Tao Xia, Yao Shi,2 College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, 30027 2 Key Laboratory of Biomass Chemical Engineering of Ministry of Education, Zhejiang University, Hangzhou, 30027 *Email: yihezj@zju.edu.cn Tuning chemical reactions with external electric field (Efield) has long been a desirable goal for researchers. Molecular simulation methods based on reactive force fields [,2] (ReaxFF) is recently developed for the study of chemical reactions in large systems at a micro-scale. To this end, the effects of Efields on chemical reactions were studied with the ReaxFF MD simulations by using the oxidation of toluene as a model system. We observed that Efields may greatly enhance the oxidation rate of toluene. The initial reaction time of toluene is also reduced remarkably in Efields. A stronger Efield leads to a faster oxidation rate of toluene. Further studies reveal that the applying of Efields may results in the oxidation of toluene at 200 K which is otherwise not able to happen when Efield is not at present. The oxidation rate of toluene at 200 K in Efield is comparable with the oxidation rate of toluene at 2900 K when Efield is not applied. In addition, Efield was observed to significantly enhance the occurrence of the initial radical generation for different pathways of toluene oxidation but it does not seem to favor any of the pathways. Finally, Efields do not seem to enhance the polarization of toluene during its transition state, which suggests that a polarizable charge equilibration method (QEq) method might be needed to take the effects of Efields into consideration. Fig. Evolution of the toluene and oxygen molecules at density ρ = 0.5, 0.35 g/cm 3, Efield = 0, 0.2 V/Å (ReaxFF NVT-MD simulation, T = 2500 K, toluene/oxygen = :00). Keywords: molecular dynamics; ReaxFF; electric field; toluene References: [] Tan, S.; Xia, T.; Shi, Y.; Pfaendtner, J; Zhao, S.; He, Y. Sci. Rep. 207, 7: 70. [2] Chenoweth, K.; van Duin, A. C. T.; Goddard, W. A. J. Phys. Chem. A 2008, 2: 040. 98

O-4-09 Ti-MWW 分子筛催化氧化硫化物的量子化学研究 王寒露,*, 余梅 广东石油化工学院, 茂名,525000 *Email: 8630332@qq.com 氧化脱硫方法由于其温和的反应条件, 设备简单等优势目前成为国内外研究热点 钛硅分子筛作为一种理想的固体催化剂, 在石油化工催化氧化领域表现出瞩目的成绩 MWW 型分子筛的孔道结构独特, 具有两套相互独立的 0 元环 (0MR) 正弦孔道和 2 元环 (2MR) 超笼体系, 超笼之间通过 0MR 窗口彼此相连, 在晶体的外表面分布着 2MR 杯穴 相较于 TS- 和 Ti-Beta 分子筛, 具有这种拓扑结构的 Ti-MWW 分子筛对大小分子均表现出优良的催化氧化性能 本文采用 ONIOM2(ωB97X-D/ 6-3+g(d,p):PM6) 方法,7T/65T 模型研究了含缺陷位 Ti-MWW 分子筛 (Ti-MWW-d) 催化氧化芳香性硫化物 (Fig.), 如噻吩, 苯并噻吩及二苯并噻吩的反应机理 首先, 确定了 [Ti(OSi)4] 物种优先落位于 T 位 Ti-MWW-d 吸附 H2O2 后经历质子转移生成单齿超氧化物 Int_a 研究表明其结构异构体双齿超氧化物 Int_b 反应性更强 因此采用 Int_b 进行下一步反应 Int_b 吸附硫化物后经历过渡态 TS_2 形成亚砜产物 Int_3 亚砜继续氧化成砜经历过渡态 TS_3 这些氧化脱硫反应的决速步为亚砜生成步骤 我们也研究了无缺陷分子筛 (Ti-MWW-p) 催化氧化芳香性硫化物的反应机理, 反应也分两步进行, 首先生成亚砜然后生成砜 相较于 Ti-MWW-d 的氧化脱硫反应, 表观活化能明显升高 同时, 我们也研究了无分子筛催化剂的裸反应 : 即硫化物与 H2O2 反应 其表观活化能比 Ti-MWW-d 和 Ti-MWW-p 都要高 计算结果有助于从分子水平上理解 Ti-MWW 型分子筛催化氧化脱硫反应机理 Fig. 缺陷位和无缺陷的 Ti-MWW 分子筛活性中心及硫化物 关键词 :Ti-MWW; 分子筛 ; 氧化脱硫 ; 量子化学 ; 反应机理 基金项目 : 国家自然科学基金 (2403038), 广东省自然科学基金 (205A03033892), 广东省高等学校优秀青年教师培养计划 (YQ2056) 参考文献 [] Yang, G.; Zhou, L.; Liu, X.; Han, X.; Bao, X. Chem.-Eur. J. 20, 7: 64 [2] Wu, P.; Tatsumi, T.; Komatsu, T.; Yashima, T. Chem. Lett. 2000, 29: 774. [3] Zhou, W.-J.; Wischert, R.; Xue, K.; Zheng, Y.-T.; Albela, B.; Bonneviot, L.; Clacens, J.-M.; De Campo, F.; Pera-Titus, M.; Wu, P. ACS Catal. 203, 4: 53. 99

O-4-0 五唑阴离子形成和分解机理的理论计算研究 尉涛 *, 马义丁, 来蔚鹏, 刘英哲, 葛忠学, 任淦 氮氟化工资源有效利用国家重点实验室, 西安近代化学研究所, 西安市雁塔区电子城丈八东路 68 号,70065 *Email: fischer@wo.cn 最近五唑阴离子的合成取得了重大突破 [, 2] 它是继叠氮阴离子 [3] 和五氮阳离子 [4] 之后第三个宏观量级别的均聚氮结构 最近几年我们致力于亚稳态富氮物质的理论计算研究 [5-9] 因此在第一时间开展了五唑阴离子形成和分解的相关势能面计算 多种量子化学方法计算结果表明 : 芳基五唑形成阴离子自由基比较困难, 它是影响了五唑阴离子形成的决定因素 ; 芳基五唑释放氮气和其碳氮键裂解形成五唑阴离子的过程存在竞争关系 ; 五唑阴离子能够进一步被氧化, 形成更稳定的五唑氧化物 本研究提出的观点有助于进一步理解五唑阴离子形成和分解机理, 其中一些还需未来实验和更高级别理论计算的印证 关键词 : 聚氮 ; 量子化学 ; 反应机理参考文献 [] Zhang, C.; Sun, C.; Hu, B.; Yu, C.; Lu, M. Science 207, 355: 374. [2] Zhang, C.; Yang, C; Hu, B.; Yu, C.; Zheng, Z.; Sun, C. Angew. Chem. Int. Ed. 207, 56: 452. [3] Ugi, I. Heterocycl. Chem. 964, 3: 373. [4] Christe, K. O.; Wilson, W. W.; Sheehy, J. A.; Boatz, J. A. Angew. Chem. Int. Ed. 999, 38: 2004. [5] Yu, T.; Liu, Y.-Z.; Haiges, R.; Christe, K. O.; Lai, W.-P.; Wu, B. RSC Adv. 204, 4: 28377. [6] Yu, T.; Wu, B. Inorg. Chem. Front. 205, 2: 99. [7] Yu, T.; Lai, W.-P.; Liu,Y.-Z.; Wu, B.; Ge, Z.-X.; Bu, J.-H. Comput. Mater. Sci. 206, 23: 3. [8] 刘英哲, 来蔚鹏, 尉涛, 葛忠学, 徐涛, 骆艳娇, 尹世伟含能材料, 207, 25(2): 00. [9] 刘英哲, 来蔚鹏, 尉涛, 葛忠学, 骆艳娇, 徐涛, 尹世伟含能材料, 207, 25(7): 552. 200

O-4- The catalytic mechanism, improvement and design of nanozymes Hui Wang, Xinghua Shi * CAS Key Laboratory of Nanosystem and Hierarchial Fabrication, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 0090, P.R. China *Email: shixh@nanoctr.cn As the next-generation artificial enzymes, nanozymes show many advantages including the high catalytic activity of natural enzyme, the unique prosperity of nanomaterials, good stability and Low cost. The widely potential applications make them an emerging field bridging nanotechnology and biology. Design and synthesis of nanozymes with higher catalytic activity have draw people s interests in many fields. Many new nanozymes have been developed, but a little atomic/molecular-level information is obtained due to the limitation of the experimental techniques. The lack of fundamental knowledge for the chemistry substantializing the experimental observations and practical applications limits the rapid development of nanozymes. Here, we experimentally and theoretically investigate the catalytic reaction mechanism on the surface of metal xoide and self-assembled guanine-rich DNA/histidine-rich peptide components, that mimicks the active site and peroxidative activity of hemoproteins. These studies shed new light on the design and improvement of nanozymes. Fig. The catalytic mechanism of self-assembled guanine-rich DNA/histidine-rich peptide/hemin and Fe 3O 4 nanozymes Keywords: Nanoenzyme/catalysts H 2O 2 Surface Reaction mechanisms A first-principles study References: [] Q. Liu, H. Wang, X. Shi, Z.-G. Wang, B. Ding, ACS nano, 207,, 725 7258. [2] K. Fan, H. Wang, J. Xi, Q. Liu, X. Meng, D. Duan, L. Gao, X. Yan. Chem. Commun., 207, 53, 424-427. 20

O-4-2 封闭球腔内氢键流体的界面张力研究 顾芳,*, 李江涛, 王海军,* 河北大学化学与环境科学学院, 河北省保定市五四东路 80 号,07002 *Email: fanggu@hbu.edu.cn, whj@hbu.edu.cn 众所周知, 受限于介观尺度下的流体与体相流体之间的物理化学性质有着显著的区别. 因而可以通过考察受限尺度 温度 分子间相互作用等对流体的物理行为进行调控. 本文利用经典流体的密度泛函理论研究了封闭球形微腔内的氢键流体的界面张力问题. 具体地, 首先根据密度泛函理论给出体系的巨势泛函, 然后利用巨势最小化得到受限流体的平衡密度分布, 进而利用所得平衡密度分布及体相自由能计算了不同条件下流体 微腔的界面张力. 进一步基于所得结果详细地考察了微腔尺寸 流体体相密度 氢键作用 ( 氢键能量及官能度 ) 对体系界面张力的影响, 研究旨在为相关实验研究提供理论线索. Fig. The effect of HB energy on interfacial tension under various conditions of closed system. 关键词 : 氢键流体 ; 纳米微腔 ; 界面张力 ; 经典流体的密度泛函理论. 参考文献 [] Gray, C. G., Gubbins, K. E., Joslin, C. G. Theory of Molecular Fluids, Vol. 2., OUP, NY, 20 [2] Fujikawa, S.; Yano, T.; Watanabe, M. Vapor-Liquid Interfaces, Bubbles and Droplets. Springer, 20. [3] Wang L. Y., Gu F., Wang H.J., Sun Z.L. J. Phys. Chem. B, 207, 2, 242-252. 致谢 : 感谢国家自然科学基金 (2374028 2306034) 河北省自然科学基金(B2042003) 河北省高层次人才资助项目 (A2060500) 河北省青年拔尖人才项目及河北省普通高校青年拔尖人才计划 (BJ20707) 的资助. 202

O-4-3 Co2Bn (n = - 8) 团簇几何结构的密度泛函理论研究 吴夏, 2, 魏征, 2 安庆师范大学化学化工学院, 安庆,2460 2 光电磁功能材料安徽省重点实验室, 光电磁功能配合物和纳米配合物安徽省重点实验室, 安庆,2460 *Email: xiawu@aqnu.edu.cn 摘要 : 近年来, 由于过渡金属 (TM) 掺杂 Bn 团簇可能阐明的基本化学键性质, 及在光学 能源以及储存氢气等方面的广泛应用 [ 3], 针对其结构的研究已经吸引了相当大的关注. 硼原子的缺电子性使其具有了仅 次于碳原子的多样性结构, 从而形成六元环 七元环的双锥体结构以及八元环 九元的环分子轮 (molecular wheels) 结构, 甚至形成类似于鼓的结构. 受到小型环状和管状的双金属掺杂硼团簇的启发, 采用密度泛函 理论, 在 B3LYP / 6-3 + G(d) 水平下对 Co2Bn (n = - 8) 团簇的几何结构 相关稳定性 电子性质和磁性 进行了的研究. 研究结果表明 : 当 n 5 时, 团簇的最低能量结构为平面结构. 当 6 n 8 时, 团簇的最 低能量结构为立体结构. 对团簇的平均原子结合能 二阶差分能量 HOMO-LUMO 能隙 垂直电子亲和能 垂直电离能和化学硬度分析结果表明,Co2B7 具有幻数特征. 对 Co2Bn (n = - 8) 团簇的总磁矩计算表明其 和团簇的自旋态有很强的关系, 而且团簇的总磁矩主要由钴原子的 3d 轨道所贡献. 关键词 :Co2Bn 团簇 ; 稳定性 ; 密度泛函理论 ; 磁性 参考文献 [] 包括, 马帅领, 徐春红, 崔田. 物理学报, 207, 66(3): 03604. [2] Li, W. L.; Jian, T.; Chen, X.; Li, H. R.; Chen, T.T.; Luo, X. M.; Li, S. D.; Li, J.; Wang, L. S. Chem. Commun. 207, 53: 587. [3] Jian, T.; Li, W. L.; Chen, X.; Chen, T. T.; Lopez, G. V.; Li, J.; Wang, L. S. Chem. Sci. 206, 7: 7020. [4] 沈艳芳, 徐畅, 黄敏, 王海燕, 程龙玖. 化学进展, 206, 28(): 60 [5] Li, W. L.; Jian, T. ; Chen, X. Chen, T. T.; Lopez, G. V.; Li, J.; Wang, L. S. Angew. Chem. Int. Ed. 206, 55: 7358. [6] 张丽. 原子与分子物理学报, 206, 33(6): 26. [7] Jian, T.; Li, W. L.; Popov, I. A.; Lopez, G. V.; Chen, X.; Boldyrev, A. I.; Li, J. Wang, L. S. J. Chem. Phys. 206, 44: 5430. [8] Popov, I. A.; Jian, T.; Lopez, G. V. Boldyrev, A. I.; Wang, L. S. Nat. Commun. 205, 6: 8654. [9] Zhang, L. N.; Jia, J. F.; Wu, H. S. Chem. Phys. 205, 459: 3. [0] Pham, H.T.; Nguyen, M.T. Phys. Chem. Chem. Phys. 205, 7: 7335. [] 阮文, 余晓光, 谢安东, 伍冬兰, 罗文浪. 物理学报, 204, 63(24): 2430. [2] Xie, S. Y.; Li, X. B.; Tian, W. Q.; Chen, N. K.; Zhang, X. L.; Wang, Y. L.; Zhang, S. B.; Sun, H. B. Phys. Rev. B. 204, 90: 035447. [3] Li, F.; Zhao, J. J.; Chen, Z. F. Nanotechnology. 200, 2: 34006. 基金项目 : 国家自然科学基金项目 (2203002) 安徽高校自然科学研究项目重点项目 (KJ207A349) 作者简介 : 吴夏, 男, 安徽安庆人, 博士, 安庆师范大学化学化工学院副教授, 主要从事化学信息学 分子模拟等研究与教学工作 E-mail: xiawu@aqnu.edu.cn 203

O-4-4 烃类转化反应机理研究 赵志坚 * 天津大学化工学院天津市津南区海河教育园雅观路 35 号 300350 Email: zjzhao@tju.edu.cn 烃类转化反应是石油工业中的一类重要反应 本项研究从经典的 Pt 系催化剂出发, 以乙烯为模型分子, 研究了 Pt 表面脱氢 加氢 氢迁移 C-C 键断裂等烃类转换基本反应的反应机理及规律 通过 DFT 计算 动力学蒙特卡洛模拟 红外光谱模拟等综合手段, 修正了前人提出的乙烯转换反应机理 在此基础上, 研究了三类重要的烃类转化过程 :() 环烷烃开环反应 : 计算结果表明, 产物选择性取决于 C-C 键断裂反应的活性 通过调变催化剂颗粒大小, 改变平台位与台阶位的比例, 实现催化产物的选择性调节 (2) 丙烷脱氢反应 : 通过调变合金体系的 d 带中心位置, 平衡该反应活性与选择性的关系 实现增加目标产物丙烯选择性的同时, 提高催化剂的稳定性 (3) 甲烷活化反应 : 通过密度泛函理论计算, 明确了分子筛体系中甲烷活化的反应位点 ; 提出了完整的甲烷部分氧化制甲醇三步法的催化反应机理 关键词 Pt 基催化剂, 烃类转化, 环烷烃开环, 丙烷脱氢, 甲烷部分氧化 参考文献 Zhao, Z.-J.; Chiu, C.; Gong, J. Chem. Sci. 205, 6, 4403 4425. Zhao, Z.-J.; Moskaleva, L. V.; Rösch, N. J. Catal. 202, 285, 24 33. Zhao, Z.-J.; Moskaleva, L. V.; Rösch, N. ACS Catal. 203, 3, 96 205. Zhao, Z.-J.; Moskaleva, L. V.; Rösch, N. J. Catal. 203, 299, 46 49. Liu, G.; Zeng, L.; Zhao, Z.-J.; Tian, H.; Wu, T.; Gong, J. ACS Catal. 206, 6, 258 262. Zhao, Z.-J.; Kulkarni, A.; Vilella, L.; Nørskov, J. K.; Studt, F. ACS Catal. 206, 6, 3760 3766. Zhao, Z.-J.; Mu R.; Wang, X.; Gong, J. Langmuir, 207, DOI: 0.02/acs.langmuir.7b00788 204

P--00 Exploring functions of long noncoding RNAs across multiple cancers through co-expression network Suqing Li, Qingyue Li, Menglong Li, Xuemei Pu,*, Leming Shi 2,* Department of Chemistry, Sichuan University, Chengdu, 60064 2Center for Pharmacogenomics, School of Life Sciences, and State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, Fudan University, Shanghai, 20203. *E-mail: xmpuscu@scu.edu.cn (Xumei Pu). *E-mail: lemingshi@fudan.edu.cn (Leming Shi). In contrast to protein-coding genes, long-noncoding RNAs (lncrnas) are much less well understood, despite increasing evidence indicating a wide range of their biological functions, and possible roles in various cancers. Based on public RNA-seq datasets of four solid cancer types, we here utilize Weighted Correlation Network Analysis (WGCNA) to propose a strategy for exploring the functions of lncrnas altered in more than two cancer types, which we call onco-lncrnas. Results indicate that cancerexpressed lncrnas show high tissue specificity and are weakly expressed, more so than protein-coding genes. Most of the 236 onco-lncrnas we identified have not been reported to have associations with cancers before. Our analysis exploits co-expression network to reveal that onco-lncrnas likely play key roles in the multistep development of human cancers, covering a wide range of functions in genome stability maintenance, signaling, cell adhesion and motility, morphogenesis, cell cycle, immune and inflammatory response. These observations contribute to a more comprehensive understanding of cancer-associated lncrnas, while demonstrating a novel and efficient strategy for subsequent functional studies of lncrnas. Keywords: Long noncoding RNA; Cancers; Function; Co-expression network References: [] Li S. Q.; Li B.; et.al.; Le M. S.*, Pu, X. M.*. Sci. Rep. 207, 7:754. [2] Wang Y.; Pu, X. M., Li, M. L.*, RSC Adv. 207, 3:2046 [4] Li Z. Y.; Guo. Y. Z.*; Pu X. M.; Li M. Li.*, Sci. Rep. 206, 6: 3472 205

P--002 A joint strategy applied to explore structural feathers of intermediate states in the activation process and their selections to ligands for GPCR Tao Liang, Ran Wang, Tian Ren, Yinyu Wang, Menglong Li, Xuemei Pu,* Department of Chemistry, Sichuan University, Chengdu, 60064 *E-mail: xmpuscu@scu.edu.cn (Xumei Pu). It was already suggested by experiments that there should be multiple intermediate states in the activation process for G-protein-coupled receptors (GPCRs). However, the intermediate states are very short-lived and hardly captured by the experiments, leading to very limited understanding of their structural features and drug-efficacies. In this work, a novel joint-strategy of targeted molecular dynamics simulation (TMD), conventional molecular dynamics (CMD) simulation and virtual screening is developed to address the problems. The results from ten intermediate conformations obtained from the work reveal that the ligand pocket is very unstable and fluctuates between the inactive state and the active one in the case of ligand-free, in particular for ECL2 as a gate-keeper of the ligand-binding. The ligand-binding site could be stable in the active state with a small volume and a completely closed ECL2, only when the G protein-binding region is fully activated. In addition, the activations of the ligand-binding pocket and G protein-binding site are relatively independent and exhibit a loose allosteric coupling, which contributes to the existence of multiple intermediate conformations. Interestingly, the screening performance to the agonists does not increase with increasing the overall activity of the intermediate state, but dependent on the activated extent of the ligand-pocket. The receptor is prone to bind the agonist when closing ECL2 and reducing ligand-binding pocket volume, while it is more favorable for binding the antagonist when opening ECL2 and increasing the pocket volume. These observations added to previous studies could help us better understand the activation mechanism of GPCRs and provide valuable information for drug design. Keywords: G-protein coupled receptor; Molecular dynamics simulations; Activation; Intermediate state; Virtual screening References: [] Xiao X.; Zeng X.; Yuan Y.; Pu, X. M.*. Phys. Chem. Chem. Phys. 205, 7(4):252. [2] Gao, N.; Liang, T.; et.al. Pu, X. M.*. Phys. Chem. Chem. Phys. 206, 8: 2942 [3] Zeng, X. J.; Zhang, L. Y.; et.al. Pu, X. M.*, Li, M. L.*, Sci. Rep. 206, 6: 24065 [4] Zhang, L. Y.; Li, Y. Z.; et.al. Li, M. L.; Pu, X. M.* Sci. Rep. 206, 6:36838 206

P--003 数据挖掘辅助化学实验设计算法对比畅东平, 张庆 2, 卢凯亮, 陆文聪,3* 上海大学材料基因工程研究院,200444 2 上海大学材料科学与工程学院,200444 3 上海大学理学院化学系,200444 *Email: Cdp_SHU@shu.edu.cn 本工作运用三种不同的数据挖掘算法 [] 对钴铝层状双金属氢氧化物 (Co-Al LDHs) 氟离子吸附容量建立定量模型, 复合材料的钴元素的摩尔比 (Co%) 吸附剂的剂量 (M) 溶液的 ph 值 (ph) 溶液的氟离子浓度 (C) 为主要特征变量 [2] XGBoost 和 GBR 是近几年来被提出的新型集成学习算法, 计算结果表明, Xgboost/GBR 算法的结果优于 SVR 算法的结果 其中不同算法的均方根误差 (RMSE) 及实验值和预报值的相关系数 (R) 见下表 同时, 设计样本基于三种不同的模型 (Xgboost, GBR, SVR) 预报的氟离子吸附容量与验证实验结果相一致 因此, 本工作所建立的回归模型有望在氟离子吸附容量预报工作中得到进一步的应用, 同时, 也对不同算法的模型优劣进行了比较, 便于得出更加可靠的结论 Xgboost GBR SVR RMSE 0.5299 0.5342 0.755 R 0.9338 0.9348 0.8790 Fig. Performance of three different algorithm Experimental versus predicted fluoride adsorption capacity 关键词 : 数据挖掘 ; 集成学习 ;XGBoost;GBR; 参考文献 []Xiong, P.; Ji, X.; Zhao, X.; Lv, W.; Liu, T.; Lu, W. Chemometr Intell Lab. 205, 44:-6. [2]Zhao, X.; Zhang, L.; Xiong, P.; Ma, W.; Qian, N.; Lu, W. Micropor Mesopor Mat. 205, 20:9-98. [3]Tianqi Chen;Carlos Guestrin. XGBoost: A Scalable Tree Boosting System. 22nd SIGKDD Conference on Knowledge Discovery and Data Mining, 206 [4] J. Friedman.Greedy Function Approximation: A Gradient Boosting Machine.The Annals of Statistics, Vol. 29, No. 5, 200. 207

P--004 香豆素类抗癌药物的定量构效关系研究徐跃龙, 朱丽娟, 张琼月, 方子涵, 陈可先 * 浙江工商大学食品与生物工程学院, 浙江杭州,3008 *Email: ckx_chem@zju.edu.cn 香豆素 (coumarin) 类化合物往往具有抗菌 抗癌 抗凝血等广泛的生物活性 [,2], 其类似物又具有容易合成的特点 大量的研究从香豆素骨架结构出发去设计和开发具有抗肿瘤活性的衍生物或类似物 [3,4] 目前, 该类药物的设计主要通过总结香豆素类化合物对 SKOV3 HCT6 和 HepG2 等各种癌细胞的生物活性, 得出各类官能团的修饰规律, 从而设计出具有潜在抗癌活性的新型药物 [3,4] 从高效药物开发的角度, 该类方法通常具有一定的盲目性, 而且开发周期常, 成本高 我们以最新合成的系列 4- 取代香豆素类抗癌药物为研究对象 [3], 使用 Material Studio 7.0 软件中的 QSAR 模块计算电子 能量 结构 热力学 空间等各类微观结构参数, 采用 Hierarchical Cluster Analysis 聚类方法将其分类为训练集和预测集, 再用遗传函数算法 (GFA ) 构建其二维定量结构与活性关系 (2D-QSAR), 所建模型均通过了显著性检验 [5,6], 其中 R 2 均大于 0.90,R 2 CV 接近 0.90, 且预测集预测活性与真实活性误差较小, 因此具有良好的预测可靠性 计算表明,4- 取代香豆素类抗癌药物对 HepG2 细胞活性的影响主要受到电拓扑状态描述符 (S_dCH2) 空间描述符 (Shadow area 和 Jurs-RPCG) 和结构描述符 (Molecular area) 的影响, 而且 Molecular area 对活性贡献占 90.9%,Shadow area fraction: YZ plane 占 9.09% 在此基础上, 我们还根据生物电子等排体规则, 设计了几种新药, 部分药物可能具有潜在的合成价值 (Fig. ) Fig. Predicted activity of newly designed coumarin compounds 关键词 : 香豆素 ; 抗癌活性 ;QSAR; 统计方法 参考文献 [] Thakur, A.; Singla, R.; Jaitak, V. Eur. J. Med. Chem. 205, 0: 476. [2] Basanagouda, M.; Jambagi, V. B.; Barigidad, N. N.; et al. Eur. J. Med. Chem. 204, 74: 225. [3] Cao D., Liu, Y.; Yan, W.; et al. J. Med. Chem. 206, 59: 572. [4] Wang, R.; Chen, C.; Zhang, X.; er al. J. Med. Chem. 205, 58: 473. [5] Golbraikh, A.; Tropsha, A. J. Mol. Graph. Model. 2002, 20: 269. [6] Chen, K.; Li, Z.; Xie, H.; et al. Eur. J. Med. Chem. 2009, 44: 4367. 208

P--005 白蛋白与有机磷加合物位点识别及结构性质研究丁俊杰 *, 孙凤娟, 丁晓琴, 王红梅 * 北京药物化学研究所, 北京,02205 *Email: djj224@63.com; wanghongmei@dicp.ac.cn 有机磷化合物与人或动物体内蛋白质作用形成加合物, 是检测和推断其是否中毒的重要依据 本文通过高分辨的质谱检测方法, 研究了沙林等 7 种有机磷化合物对人 牛 大鼠 兔等种属的白蛋白体外染毒的加合物及其位点, 得出 4 个白蛋白与有机磷加合物位点,4 个作用位点是 6 个酪氨酸 7 个赖氨酸 个丝氨酸 应用分子模拟技术, 对 4 个作用位点进行了结构性质研究 由于位点的活性受立体空间效应和静电效应影响较大, 因此我们以白蛋白的结构性质为基础, 从立体空间和静电效应对作用位点进行预测分析, 研究结果为实验数据提供理论依据 有机磷与白蛋白相互作用是由酪氨酸 丝氨酸和赖氨酸中的氧和氮原子对有机磷中的磷原子发生亲核进攻反应 为了研究位点的活性和结构性质, 从立体空间和静电效应等 4 个方面进行模拟计算 : 预测作用位点残基溶剂可及表面积 (SAS);2 预测白蛋白的立体空间口袋 ;3 计算作用位点残基与其他正电荷残基形成的离子对情况 ;4 计算作用位点残基与其他残基间的非键相互作用 由计算结果可见, 除了 Y84 和 K44 外, 其他 2 个残基均处于溶剂暴露状态, 由于是对蛋白的晶体结构进行计算, 因此 2 个残基在溶液中构象变化的动态情况下, 很可能是处于暴露状态 此外, 对蛋白的立体空间口袋进行了预测,4 个作用位点均在口袋里边或者在蛋白表面, 在立体空间上满足反应条件,4 个位点在蛋白中的三维空间位置见图 酪氨酸 丝氨酸侧链氧原子与正电荷原子相距 6Å 之内, 将产生静电作用, 使氧原子 氮原子亲核性增强 此外, 作用位点酪氨酸和赖氨酸的侧链与其他残基的非键相互作用, 将增强其亲核性 综合计算结果分析,4 个作用位点, 从结构性质本身考察, 在立体空间和静电效应上均满足反应条件, 通过与其他残基形成离子对或非键相互作用, 增强亲核性, 利于对有机磷化合物进行亲核性进攻, 在立体空间上处于暴露状态或者位于蛋白空腔口袋周围及蛋白表面 图 白蛋白的三维结构及 4 个作用位点在蛋白中的空间位置 ( 白蛋白以红色的飘带表示, 蛋白的空间口袋以绿色点形图表示,4 个作用位点以黄色的 CPK 模型表示 ) 关键词 : 白蛋白 ; 有机磷 ; 加合物位点 ; 分子模拟 参考文献 [] R. W. Read, J. R. Riches, J. A. Stevens, S. J. Stubbs, R. M. Black. Arch. Toxicol. 200, 84, 25 36. [2] J. L. S. Sporty, S. W. Lemire, E. M. Jakubowski, J. A. Renner, R. A. Evans, R. F. Williams, J. G. Schmidt, M. J. van der Schans, D. Noort, R. C. Johnson. Anal. Chem. 200, 82, 6593 6600. 209

P--006 蛋白质机器与配体分子结合动力学的高效计算模拟及其应用杜宇, 王任小 * 中国科学院上海有机化学研究所, 上海市,200032 *Email: wangrx@mail.sioc.ac.cn 在新药研发的早期阶段, 除了评价化合物对靶标的亲和力和选择性外, 还有另外一个重要的因素, 即复合物的动力学性质, 它与体内药效和安全性密切相关 药物设计的初期常常选用基于热力学的参数进行合理设计, 比如亲和力 但是亲和力并不能完全决定药物的作用时效 面对每年高昂的新药研发费用和严重的药物损耗而上市终止的情况, 更加合理高效的药物设计才能帮助提高药物的针对性和临床表现 药物与受体的结合与解离的速率越来越被研究人员认为直接影响药物的效力和安全性 理解药物和受体的结合动力学的分子机理还存在很多挑战 我们的课题将开发可以让研究人员更加方便使用的基于结合动力学的虚拟筛选的方法和工具 这些工具将会帮助研究者在药物发现早期决策药物候选分子是否安全有效 关键词 : 药物结合热力学 ; 药物结合动力学 ; 药物设计方法 ; 分子对接 20

P--007 靶标结构驱动的新烟碱类化合物的蜂毒机制研究许晓颖, 杨朝凯, 路星星, 张晋陆, 顾凌郡, 段红霞 * 中国农业大学理学院, 农药分子设计与发现实验室 (PMDD) 北京市海淀区圆明园西路 2 号, 邮编 :0093 *Email: hxduan@cau.edu.cn 新烟碱类杀虫剂由于高效 广谱 对脊椎动物安全等特征, 被广泛应用于现代农业害虫的防治 然而最近有研究发现, 新烟碱杀虫剂对生态环境中的有益昆虫蜜蜂的生存产生影响, 主要是干扰蜜蜂的行为 繁殖以及免疫力, 导致自然界中蜜蜂种群数量的下降 为了揭示新烟碱类化合物对蜜蜂作用的分子机制, 进而指导设计和开发具有高活性低蜂毒特征的新型杀虫剂, 本文选取烟碱乙酰胆碱受体结合蛋白 (3C79) 为模板, 利用同源模建方法建立了靶标昆虫棉蚜的 nachr (Agα/ratβ2) 和非靶标昆虫意大利蜜蜂 nachr (AmeIα8/ratβ2) 的三维结构模型 [], 运用分子对接技术, 研究了商品化新烟碱化合物 硝基缩氨基胍类化合物 [2] 以及基于靶标结构虚拟筛选的化合物 [3] 对棉蚜和蜜蜂 nachr 蛋白的分子间互作模式特征 结果发现小分子配体与受体蛋白中的关键氨基酸残基主要以氢键 卤键以及 π-π 堆积作用产生结合效应 进一步基于靶标蛋白结构揭示了这些化合物具有高杀蚜 低蜂毒特征的分子机制, 通过构建基于靶标结构的化合物筛选模型, 提出氢键条数 6 氨基酸数目 3, 和 R 避免与蛋白结合腔中 TRP85 形成 π-π 共轭, 可用于低蜂毒化合物的筛选 这一研究揭示了决定化合物高活性低蜂毒机制的关键氨基酸和小分子药效片段, 为后续高活性低蜂毒化合物的结构改造提供理论指导 (A) (B) (C) 图 (A) AmeIα8/ratβ2 三维结构模型 ;(B) Agα/ratβ2 三维结构模型 (C) 氨基酸导向的高活性低蜂毒化合物的构效特征 关键词 : 烟碱乙酰胆碱受体, 新烟碱类杀虫剂, 低蜂毒, 氨基酸导向构效关系, 筛选模型 参考文献 [] 姚香梅, 新烟碱类杀虫剂对靶标和非靶标昆虫乙酰胆碱受体毒理学特性研究 [D], 北京, 中国农业科学院植物保护研究所, 博士后研究工作报告,205 年 7 月 [2] 周子原, 硝基缩氨基胍类杀虫剂的设计与合成及生物活性测定 [D], 北京, 中国农业大学, 硕士学位论文,203 年 6 月. [3] 张晋陆, 基于昆虫烟碱乙酰胆碱受体结构的新型化合物的设计与筛选 [D], 北京, 中国农业大学硕士学位论文,206 年 5 月 2

P--008 HawkRank: A New Scoring Function for Protein-Protein Docking Based on Weighted Energy Terms Ting Feng, Tingjun Hou,2,* College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 30058 2 State Key Lab of CAD&CG, Zhejiang University, Hangzhou, 30058 *Email: tingjunhou@zju.edu.cn Deciphering the structural determinants of protein-protein interactions (PPIs) is essential to gain a deep understanding of many important biological functions in the living cells. Computational approaches for the structural modeling of PPIs, such as protein-protein docking, are quite needed to complement existing experimental techniques. The reliability of a protein-protein docking method is dependent on the ability of the scoring function to accurately distinguish the near-native binding structures from a huge number of decoys. In this study, we developed HawkRank, a novel scoring function designed for the sampling stage of protein-protein docking by summing the contributions from several energy terms, including van der Waals potentials, electrostatic potentials and desolvation potentials. First, based on the solvation free energies predicted by the Generalized Born model for ~800 proteins, a SASA (solvent accessible surface area)-based solvation model was developed, which can give the aqueous solvation free energies for proteins by summing the contributions of 2 atom types. Then, the van der Waals potentials and electrostatic potentials based on the Amber ff4sb force field were computed. Finally, the HawkRank scoring function was derived by determining the most optimal weights for five energy terms based on the training set. Here, MSR (Modified Success Rate), a novel protein-protein scoring quality index, was used to assess the performance of HawkRank and three other popular protein-protein scoring functions, including ZRANK, FireDock and ddfire. The results show that HawkRank outperformed the other three scoring functions according to the total number of hits and MSR. Keywords: Protein-protein docking; Scoring function; Desolvation potentials; van der Waals potentials ; Electrostatic potentials; Binding free energy 22

P--009 Structure-based design and synthesis of L858R/T790M selective epidermal growth factor receptor inhibitors for NSCLC Lingfeng Chen, #, Weitao Fu, 2, #, Chen Feng, #, Rong Qu 3, Linjiang Tong 3, Hua Xie 3, Jian Ding 3, *, Zhiguo Liu, *, Guang Liang, * Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China 2 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 30058, China 3 Division of Anti-Tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 20203, China * Email: wzmcliangguang@63.com Mutated epidermal growth factor receptor (EGFR) is a major driver of non-small cell lung cancer (NSCLC). The EGFR T790M secondary mutation has become a leading cause of clinically-acquired resistance to gefitinib and erlotinib. Herein, we present a structure-based design approach to increase the potency and selectivity of the previously reported reversible EGFR inhibitor 7, at the kinase and cellular levels. Three-step structure-activity relationship exploration led to promising compounds 9e and 9h with unique chemical structure and binding mode from the other third-generation tyrosine kinase inhibitors. In a human non-small cell lung cancer xenograft model, 9e and 9h exhibited dose-dependent tumor growth suppression without evidence of toxicity. These selective inhibitors may potentially be drug candidates for EGFR T790M -driven NSCLC. Fig. Table of Contents graphic Keywords: epidermal growth factor receptor; tyrosine kinase inhibitors; non-small cell lung cancer; T790M; mutant-selective. References: [] Fu W, Chen L, Wang Z, et al. Phys Chem Chem Phys, 207, 9(5):3649-3659. [2] Chen L, Jin Y, Fu W, et al. ChemMedChem, 207, 2: 022-032. [3] Ying S, Du X, Fu W, et al. Eur J Med Chem, 207, 27: 885-899. 23

P--00 Inflammatory pathway network-based drug repositioning and molecular phenomics Jiangyong Gu, Lirong Chen2, Xiaojie Xu2,* Second school of clinic medicine, Guangzhou University of Chinese Medicine, No. 55, Neihuanxi Road, Guangzhou Higher Education Mega Center, Guangzhou 50006 2 College of Chemistry and Molecular Engineering, Peking University, No. 202, Chengfu Road, Beijing 0087 *Email: xiaojxu@pku.edu.cn Inflammation is a multi-component response to various injuries and protects the body to restore the tissue to its pre-injury state. Uncontrolled inflammation, especially chronic inflammation, has been regarded as a pathophysiologic basis for many diseases, including cardiovascular disease, asthma, arthritis, and cancers. However, little is known about the causes of chronic inflammation and the associated molecular and cellular pathways. In this work, we constructed the pathway network of inflammation, including sub-pathways of inflammatory factors. Pathway-based network efficiency and network flux were adopted to evaluate drug efficacy. By using approved and experimentally validated anti-inflammatory drugs as training sets, a predictive model was built to screen potential anti-inflammatory drugs from approved drugs in DrugBank. This drug repositioning approach would bring a fast and cheap way to find new indications for approved drugs. Moreover, molecular phenomics profiles of the expression of inflammatory factors will provide new insight into drug mechanism of action. Fig. Molecular phenomics profile. The phenotypic correlation were calculated as the covariance between each pair of datasets of EC50s of all anti-inflammatory drugs. Keywords: Inflammation; pathway network; network efficiency; drug repositioning; molecular phenomics References: [] Gu, J.; Crosier, P.; Hall, C.; Chen, L.; Xu. J. Mol. BioSyst. 206, 2: 2777. [2] Gu, J.; Zhang, X.; Ma, Y.; Li, N.; Luo, F.; Cao, L.; Wang, Z.; Yuan, G.; Chen, L.; Xiao, W.; Xu. J. J. Cheminform. 205, 7: 9. 24

P--0 建立蛋白 - 蛋白分子对接打分函数的评价体系韩莉, 刘志海, 李嫣, 王任小 * 中国科学院上海有机化学研究所, 生命有机国家重点实验室, 上海,200032 *Email: wangrx@sioc.ac.cn 蛋白质 - 蛋白质相互作用是生命活动中许多重要进程的基础 在模拟蛋白 - 蛋白相互作用的计算方法中, 分子对接由于具有精度良好 适用性强 方便快速等优点而得以广泛的应用 目前, 已经发展起来的蛋白 - 蛋白打分函数已有十数种, 其性能难免参差不齐 因此, 需要建立一套客观 系统的方法来对这些打分函数进行评估 在本项工作中, 我们采用了三个方面的控制条件, 从 PDBbind 数据库中筛选出了包含 273 个蛋白 - 蛋白复合物的数据集 该数据集是目前相关领域内规模最大 数据质量最高的数据集 我们对四种常用的蛋白 - 蛋白打分函数的 对接能力 和 打分能力 进行了评估 对接能力 指从诱饵集中甄别出正确的结合构象的能力 评估结果显示 ( 见 Figure ),ATTRACT 和 ZRANK 对接能力相当出色, 其识别正确的复合物结合构象的概率约为 70%, 其次,dDFIRE 的正确率接近 50%,FASTCONTACT 的对接能力最差, 其正确率只有约 30% 此外, 我们计算了蛋白 - 蛋白打分函数的打分值与复合物亲合性实验数据的相关性, 即 打分能力 评估结果显示, 没有一种打分函数的打分结果与亲合性实验数据的 Pearson 相关系数超过 0.2, 即, 蛋白 - 蛋白打分函数尚不能对亲合性数据进行定量预测 本课题为进一步发展研究生物大分子相互作用的理论计算方法提供了理论依据和指导 Fig. Success rates of identifying the native binding pose among decoy binding poses for (a) ATTRACT; (b) ddfire; (c) FASTCONTACT; (d) ZRANK. 关键词 : 蛋白 - 蛋白相互作用 ; 分子对接 ; 打分函数 ; 蛋白 - 蛋白测试集 参考文献 [] Keskin O., Gursoy A., Ma B., Nussinov R. Chem. Rev. 2008, 08: 225. [2] Smith G.R., Sternberg M.J.E. Curr. Opin. Struct. Biol. 2002, 2: 28. [3] Chen C., Cui J., Lu H., Wang R., Zhang S., Shen P. Biophys. J. 2007, 92: 4304. [4] Janin J., Henrick K., Moult J., Eyck L.T., Sternberg M.J., Vajda S., Vakser I., Wodak S.J. Proteins. 2003, 52: 2. [5] Vreven T., Moal I.H., Vangone A., Pierce B.G., Kastritis P.L., Torchala M., Chaleil R., Jiménez-García B., Bates P.A., Fernandez-Recio J. J. Mol. Biol. 205, 427: 303. 25

P--02 MDBuilder: a program for the preparation of biomolecular simulations Hui Liu,#, Ye Jin 2,#, Youyong Li 2, Tingjun Hou, * College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 30058, China 2 Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 2523, China # These authors contributed equally *Email: tingjunhou@zju.edu.cn or tingjunhou@hotmail.com The preprocessed initial configuration that feeds the molecular dynamics (MD) simulations influences dramatically the outcome of the simulations. However, the popular MD simulation packages depend, to a great extent on the user s experience in the preparation of MD simulation systems. In this study, we present an easy-to-use tool called MDBuilder, a PyMOL plugin that assists researchers in building the starting structures for different popular MD simulation packages. MDBuilder is not only designed for MD beginners to overcome the steep learning curve by the straightforward menu-oriented point-and-click user interface implemented in PyMOL, but also provides an alternative way to prepare the CHARMM-force-field-based input files for other highly scalable and efficient MD simulation packages, such as NAMD and AMBER. The source code and documentation of MDBuilder can be accessed freely from https://github.com/huiliucode/mdbuilder under the GNU General Public License. It is implemented as a PyMOL plugin using the Python language. The usage is platform-independent, and it has been tested on Windows and Linux platforms. Fig. The graphical user interfaces of MDBuilder Keywords: molecular dynamics; preparation; PyMOL; MDBuilder 26

P--03 Type-I /2 型 ALK 抑制剂采用独特的 DFG-shifted 构象 抑制 ALK 抗药性突变体 孔晓天 2 潘培辰 侯廷军,2* 2 浙江大学药学院 浙江省杭州市 30058 苏州大学功能纳米与软物质学院 江苏省苏州市 2523 *Email: tingjunhou@zju.edu.cn 在本研究中 我们设计合成了一系列新型的Type-I/2型ALK抑制剂 他们不仅占据ATP结合口袋 而且 改变 DFG 的构象延伸到与ATP口袋毗邻的疏水性口袋 激酶实验和细胞试验中 化合物00-07表现出 比已经上市的crizotinib和ceritinib更为显著的抑制活性 并且对ALK的下游通路 AKT和STAT3 也有抑制 作用 此外 00-07对L96M, C56Y, R275Q and F74L ALK相关的病变细胞系有很高的灵敏度 特别 地 除了LTK和ROS, 其他33个不同家族的激酶对00-07均没有反应 显示了00-07的高度选择性 Fig. Rational design of Type/2 ALK inhibitors. Fig. 2 Inhibitory activities of the synthesized type-i/2 inhibitors. 关键词 Type-I/2 ALK抑制剂 DFG-shifted 抑制活性 抗药性突变 选择性 参考文献 [] Pan, P.; Yu, H.; Liu, Q.; Kong, X.; Hou, T. J. Med. Chem. Phys., 207, have submitted. Combating Drug-resistant Mutants of ALK with Potent and Selective Type-I/2 Inhibitors by Stabilizing Unique DFG-shifted Loop Conformation Xiaotian Kong2, Peichen Pan, Huidong Yu4, Qinglan Liu3, Tingjun Hou,2* College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 30058, China 2 Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Suzhou, Jiangsu 2523, P. R. China. In this work, we designed a series of type-i/2 ALK inhibitor that binds to not only the ATP-binding pocket but also an extended hydrophobic back pocket. The novel type-i/2 inhibitors display excellent inhibitory activity in in vitro ALK enzyme-based assay and improved efficacy than both crizotinib and ceritinib against ALK-positive cancer cells. Of note, 00-07 displayed superior sensitivity to L96M, C56Y, R275Q and F74L ALK cell line, compared to both crizotinib and ceritinib. Moreover, compound 00-07 is found highly selective towards a panel of protein kinases, and emerges as a potential drug candidate. 27

P--04 基于配体的逐级虚拟筛选方法发现新型极光激酶抑制剂孔越, 阎爱侠 * 北京化工大学化工资源有效利用国家重点实验室, 生命科学与技术学院, 北京市朝阳区北三环东路 5 号,00029 *Email: yanax@mail.buct.edu.cn 由于极光激酶家族在细胞有丝分裂中起到至关重要的作用, 且在许多恶性肿瘤中有过表达的现象, 极光激酶已成为抗肿瘤治疗的重要靶点 近些年, 科学家们开展了大量的针对极光激酶小分子抑制剂的研究 本课题中, 我们设计了一个基于配体的逐级虚拟筛选策略, 用于发现具有新型骨架特征和高抑制活性的极光激酶抑制剂 该虚拟筛选策略采用基于形状和静电筛选与基于构效关系筛选相结合的方式, 并在虚拟筛选的同时, 实现骨架跃迁 筛选得到的 24 个化合物, 经活性测试实验验证, 有 6 个化合物具有极光激酶 A 或 B 的抑制活性, 其中一个活性最强的化合物抑制活性在纳摩尔级别, 针对极光激酶 A 和 B 分别具有 8.nM 和 9nM 的抑制活性, 经优化后有望成为抑制极光激酶的先导化合物 研究结果表明, 该基于配体的逐级虚拟筛选策略成功应用于极光激酶抑制剂的筛选, 高效快速地发现新型极光激酶抑制剂, 此策略可扩展应用于其他酶抑制剂的筛选 关键词 : 极光激酶 ; 虚拟筛选 ; 形状静电筛选 ; 构效关系 28

P--05 Development of Quantitative and Qualitative Prediction Models for Chemical-Induced Respiratory Toxicity Tailong Lei, Fu Chen, Hui Liu, Huiyong Sun, Yu Kang, Dan Li, Youyong Li 3, Tingjun Hou,2,* College of Pharmaceutical Sciences, Zhejiang University, 866 Yu-hang-tang Road, Hangzhou, Zhejiang, 30058 2 State Key Lab of CAD&CG, Zhejiang University, 866 Yu-hang-tang Road, Hangzhou, Zhejiang 30058 3 Institute of Functional Nano and Soft Materials (FUNSOM), Soochow University, Block 909, 99 Ren'ai Road, Suzhou Industrial Park, Suzhou, Jiangsu 2523 *Email: tingjunhou@zju.edu.cn As a dangerous endpoint, respiratory toxicity can cause serious adverse health effects and even death. Meanwhile, it is a common and traditional issue in occupational and environmental protection. Pharmaceutical and chemical industries have a strong urge to develop precise and convenient computational tools to evaluate the respiratory toxicity of compounds as early as possible. Most of the reported theoretical models were developed based on the respiratory toxicity datasets with one single symptom, such as respiratory sensitization, and therefore these models may not afford reliable predictions for toxic compounds with other respiratory symptoms, such as pneumonia or rhinitis. Here, based on a diverse dataset of mouse intraperitoneal respiratory toxicity characterized by multiple symptoms, a number of quantitative and qualitative predictions models with high reliability were developed by machine learning approaches. First, a four-tier dimension reduction strategy was employed to find an optimal set of twenty molecular descriptors for model building. Then, six machine learning approaches were used to develop the prediction models, including relevance vector machine (RVM), support vector machine (SVM), regularized random forest (RRF), extreme gradient boosting (XGBoost), naïve Bayes (NB) and linear discriminant analysis (LDA). Among all of the models, the SVM regression model shows the most accurate quantitative predictions for the test set (q 2 ext =0.707), and the XGBoost classification model achieves the most accurate qualitative predictions for the test set (MCC of 0.644, AUC of 0.893 and global accuracy of 82.62%). The application domains were analyzed, and all of the tested compounds fall within the application domain coverage. We also examined the structural features of the compounds and important fragments with large prediction errors. In conclusion, the SVM regression model and the XGBoost classification model can be employed as accurate prediction tools for respiratory toxicity. Fig. Graphical Scheme of the QSAR Workflow Keywords: Quantitative Structure-Activity Relationship; Respiratory System Toxicity; Machine Learning; Dimension Reduction; extreme Gradient Boosting References: [] Lei, T.; Chen, F.; Liu, H.; Sun, H.; Kang, Y.; Li, D.; Li, Y.; Hou, T. Mol. Pharmaceut. 207, 4(7): 2407-242. 29

P--06 钠离子通道位点 2 与激动剂作用机制分子模拟研究李大禹, 潘里, 许磊 2, 丁俊杰, 丁晓琴 *, 侯廷军 2* 北京药物化学研究所, 北京,02205 2 浙江大学药学院, 杭州,30058 * Email: dingxiaoqin2008@26.com; 2* Email:tingjunhou@hotmail.com 钠离子通道在生物体电信号传导中起到重要的作用, 并且作用于钠离子通道的配体类型广泛, 因此对钠离子通道及其配体的结构与功能关系研究具有重要意义和应用价值 钠离子通道天然激动剂具有很强的神经毒性, 尤其作用于钠离子通道位点 2 的天然毒素 Batrachotoxin( 箭毒蛙毒素,BTX) 本文采用软件 Catalyst 的 HipHop HypoGen 方法和 Sybyl 6.5 的 CoMSIA 方法, 对作用于钠离子通道位点 2 的一些类似物进行三维药效团模型和三维定量构效关系研究 计算结果表明, 构建的药效团模型相关系数为 0.947,CoMSIA 模型的交叉验证相关系数 (CV_r 2 ) 为 0.739, 方程的相关系数 r 2 为 0.98, 两者均得到了较佳的预测模型 基于 NavAb Kv.2 的晶体结构, 采用同源建模的方法构建了 Human Nav.2 的全长 3D 结构和开放状态的孔道区域 3D 结构, 并且将搭建的模型进行了 50 ns 的分子动力学模拟, 从而对结构进行优化和修正 根据实验报道的残基突变结果以及搭建的钠离子通道 3D 结构, 采用 Induced Fit Docking 柔性对接方法得到了 Nav.2 与 BTX 复合物结构, 并采用分子动力学方法对复合物结构进行进一步优化, 分析了蛋白 - 配体间的相互作用机制, 得到了最佳的结合模式 通过分子模拟研究所得到的模型结果可用于位点 2 的作用机理探讨和活性评价, 为进一步设计合成新型钠离子通道小分子激动剂提供理论依据 图 钠离子通道位点 2 与 BTX 的相互作用模型图 关键词 : 钠离子通道 ; 箭毒蛙毒素 ;QSAR; 同源建模 ; 分子模拟 参考文献 [] Du, Y.; et al. J. Biol. Chem. 20, 286(5), 35-360. [2] Tikhonov, D. B.; Zhorov, B. S. FEBS Lett. 2005, 579, 4207 422. 220

P--07 A Novel Fragment-Based Method for GPCR Ligand Design Yan Li, Xun, Li 2, Wenge, Zhong 2, Renxiao Wang,3 * State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Lingling Road 345, Shanghai, 200032 2 Amgen Asia R&D Center, Amgen Biopharmaceutical R&D (Shanghai) Co., Ltd. Shanghai, 2020 3 State Key Laboratory of Quality Research in Chinese Medicine, Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau *Email: wangrx@sioc.ac.cn G protein-coupled receptors (GPCRs) are still the largest target class in current drug discovery. Since 2007, with the great technology breakthroughs in GPCR crystallography, ~50 GPCR complex structures have been released in PDB, covering more than 30 unique GPCRs. The abundant crystal structures provide good opportunities for structure-based rational design targeting GPCRs. We have developed a novel fragment-based method for GPCR ligand discovery by analyzing the structural information of GPCR-ligand complexes. The core idea was to extract the characteristic interaction patterns (CIPs) on the binding interfaces formed by GPCRs and their ligands. The CIPs were used as queries to screen appropriate fragments/ligands which could form similar interaction patterns with the GPCRs. The selected fragments were assembled to intact molecules by using de novo design programs, i.e. AutoT&T. We applied this method to two specific GPCR proteins (β-ar and machr) and designed ~00,000 new structures. These structures will be further analyzed and selected for experimental validations in the future. Fig. Characteristic interaction patterns extracted from β-ar-ligand complexes Keywords: Characteristic Interaction Pattern (CIP), Fragment-Based Design, GPCR Ligand References: [] Cooke, R. M.; Brown, A. J. H.; Marshall, F. H.; Mason, J. S. Drug Discov. Today 205, 20: 355. [2] Li, Y.; Liu, Z.; Han, L.; Li, C.; Wang, R. J. Chem. Inf. Model. 203, 53: 2437. [3] Li, Y.; Zhao, Z.; Liu, Z.; Su, M.; Wang, R. J. Chem. Inf. Model. 206, 56: 435. 22

P--08 计算机辅助 HIV- 整合酶 LEDGF/p75 抑制剂生物活性预测研究李杨, 阎爱侠 * 北京化工大学, 北京市朝阳区北三环东路 5 号,00029 *Email: yanax@mail.buct.edu.cn 艾滋病全称为人类免疫缺陷综合症 (AIDS), 是当今人类所共同面临的重大医学难题之一 人类免疫缺陷病毒 (HIV) 是艾滋病的病原体, 该病毒可将自身所携带的遗传基因整合到人体基因序列中, 并随着人体细胞的复制而实现自身繁殖 在这个过程中,HIV- 整合酶起到至关重要的作用 HIV- 整合酶 LEDGF/p75 位点是治疗艾滋病药物的新型靶点, 阻断整合酶和 LEDGF/p75 之间的相互作用可以有效的阻止病毒的复制和传播 [] 我们用计算机辅助药物设计的思路, 以 HIV- 整合酶 LEDGF/p75 抑制剂为研究对象, 建立了抑制剂的高低活性分类模型, 对抑制剂的生物活性进行预测研究 在模型建立过程中, 我们收集了 274 个 HIV- 整合酶 LEDGF/p75 抑制剂, 并随机分为训练集和测试集 用 CORINA Symphony 和 MACCS fingerprints 描述符, 以支持向量机 决策树 功能树和随机森林的方法建立模型 所有模型测试集预测结果均高于 70%, 其中最好的模型测试集预测结果为 8.08% 并且通过对模型的描述符分析, 我们认为抑制剂形成氢键的能力和疏水性对于它的抑制活性十分重要 [2] 关键词 :HIV- 整合酶 LEDGF/p75; 支持向量机 ; 随机森林 ; 构效关系 参考文献 : []Y. Li, S.Y. Xuan, Y. Feng, A.X.Yan, Targeting HIV- integrase with strand transfer inhibitors, Drug Discovery Today, 205, 20:435. [2] Y. Li, Y.B. Wu, A.X. Yan. Study of Structure Active Relationship for Inhibitors of HIV Integrase LEDGF/p75 Interaction by Machine Learning Methods. Molecular Informatics, 207. 222

P--09 基于 BRCA2 motif BRC8 的 RAD5 蛋白抑制剂的设计合成 刘广斌, 姜佳敏, 赵东欣 2, 马丽 2, 卢奎 3,,2* 郑州大学化学与分子工程学院, 河南郑州 45000 2 河南工业大学化学化工与环境学院, 河南郑州 45000 3 河南工程学院材料与化学工程学院河南郑州 459 *E-mail: luckyluke@haue.edu.cn 乳腺易感基因 2(BRCA2) 是一种重要的抑癌基因, 与乳腺癌的发生具有广泛的相关性, 而 BRCA2 蛋白是修复 DNA 损伤的一种关键蛋白, 并可参与多种基因表达的调控 人的 BRCA2 蛋白与其它哺乳动物的 BRCA2 蛋白具有较高的同源性, 包含 8 个序列高度保守的重复基元 (BRC), 且每个基元有 35 个氨基酸残基组成 多种癌症细胞中, 在这些基元的突变预示着 BRC 为 BRCA2 蛋白的重要功能区, 参与了多种癌症病变过程 [] 本文以 BRCA2 重复基元 BRC8 研究对象, 选取 PDBBank N0W 中 BRCA2 重复基元 BRC4 立体结构作为模板结构, 采用同源建模的方式, 建立多肽 BRC8 的立体结构, 能量优化后使用 Discovery studio 3.0 软件 ZDOCK 模块进行多肽与 RAD5 蛋白分子对接, 对接后的复合物经过能量优化后对其中的多肽进行虚拟全突变扫描, 发现 26V/H,9L/I,35L/W, 5F/Y,5F/W,26V/T,26V/E 后多肽与蛋白的结合发生显著增强 [2] 使用固相合成的方法合成七条突变肽以及 BRC8, 然后使用圆二色测定了多肽的二级结构结果发现二级结构几乎没有变化 [3] 使用 MST 测定多肽与 RAD5 蛋白的相互作用 以上结果对于基于 BRCA 的乳腺癌多肽药物的开发提供了重要的基础 a 6 4 b c d 2 e 0-2 d a f g MilliDegree -4-6 -8-0 -2 f e c b -4-6 g -8-20 90 200 20 220 230 240 250 260 270 Wavelength /nm Fig. BRC8-RAD5 complex Structure Fig.2 α-helical folding potential of BRC peptides: CD analysis 关键词 : BRCA2,BRC8,RAD5, 多肽 - 蛋白相互作用 参考文献 [] Stenen A. Narod, William D. Foulkes. Nature Reviews Cancer.2004,4:665-676. [2] Chen,Rong; Li,Li; Weng,Zhiping. Proteins.2003,52():80-87 [3] Lidia V.Najbar, David J.Craik, John D.Wade et al. Biochemistry.2000,39, 59-5920. 致谢 : 感谢国家自然科学基金 (Nos.2572046, 272054) 的资助 223

P--020 Discovery of Novel Non-Bisphosphonate FPPS Inhibitors by Multistage Docking- and Pharmacophore-Based Virtual Screening Qingzhu Liu, Shanshan Wang, Xi Li, Xueyu Zhao, Jianguo Lin, Ling Qiu * Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 24063 *Email: qiuling@jsinm.org Farnesyl pyrophosphate synthase (FPPS) is a key enzyme of the mevalonate pathway for cholesterol biosynthesis and protein prenylation, and it is the main target of nitrogen-containing bisphosphonate (N-BPs) drugs in treating skeletal and nonskeletal diseases. Although the N-BPs FPPS inhibitors are safe and effective in treating skeletal diseases and possess indirect or direct anticancer activity, the undesirable drug-like properties often limit their applications in treating nonskeletal tissues, such as poor cell-membrane permeability, poor oral bioavailability, and rapid clearance from the systemic circulation. Therefore, looking for novel non-bps inhibitors targeting FPPS constitutes a great challenge for the development of FPPS inhibitors. Structure-based virtual screening (SBVS) is a powerful technique for the early stage of drug discovery and it is able to find active compounds of novel scaffolds. In the present study, the multistage SBVS strategy by integrating docking-based and pharmacophore-based searching was employed to discover novel FPPS inhibitors. The self-docking for 35 N-BPs-hFPPS complexes was performed using AutoDock, CDOCKER, and LibDock methods to validate the accuracy of docking method, and the results showed that LibDock method could produce reliable results with the RMSD < 2 Å. The PDB 4QPF was chosen as the model for receptor-based virtual screening of novel FPPS inhibitors from the ChemDiv database, and the Lipinski s rule of five was used to screen the compounds with desirable or drug-like properties. Based on five crystal structures of hfpps-inhibitor complexes, a multicomplex-based method was used to generate a comprehensive pharmacophore model of hfpps, and the most-frequent features derived from cluster analysis were regarded as essential features to improve the activity of hfpps inhibitors. The database was further filtered according to the established pharmacophore model and the predicted drug-like ADMET properties, and the top 200-ranked candidates were selected finally. In order to avoid false positive rate of screening results, the re-docking method was further adopted by reducing the radius of docking. Combining the docking score and binding energy calculation, ten hits with novel scaffolds were identified and purchased to test the inhibition activity against hfpps. Fig. Overview of the flowchart for the discovery of FPPS inhibitors using multistage virtual screening Keywords: farnesyl pyrophosphate synthase; molecular docking; pharmacophore mapping; virtual screening 224

P--02 Forging the Basis for Developing Protein Ligand Interaction Scoring Functions Zhihai liu, Minyi Su, Li Han, Jie Liu, Qifan Yang, Yan Li,*, Renxiao Wang,2,* Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, 200032 2 Macau University of Science and Technology, Macau, People s Republic of China *Email: wangrx@mail.sioc.ac.cn In structure-based drug design, scoring functions are widely used for fast evaluation of protein-ligand interactions. Regardless of their technical difference, scoring functions all need data sets combining protein-ligand complex structures and binding affinity data for parametrization and validation. However, data sets of this kind used to be rather limited in terms of size and quality. On the other hand, standard metrics for evaluating scoring function used to be ambiguous, which do not directly reflect the genuine quality of scoring functions. In a recently published paper (Acc. Chem. Res., 207, 50 (2): pp 302-309.), we describe our long-lasting efforts to overcome these obstacles, which involve two related projects. On the first project, we have created the PDBbind database. It is the first database that systematically annotates the protein-ligand complexes in the Protein Data Bank (PDB) with experimental binding data. This database has been updated annually since its first public release in 2004. The latest release (v206) provides binding data for 679 biomolecular complexes in PDB. Data sets provided by PDBbind have been applied to many computational and statistical studies. In particular, it has become a major data resource for scoring function development. On the second project, we have established the Comparative Assessment of Scoring Functions (CASF) benchmark for scoring function evaluation. Our key idea is to decouple the scoring process from the sampling process, so scoring functions can be tested in a relatively pure context to reflect their quality. Importantly, CASF is designed to be an open-access benchmark. Binding data (Kd, Ki, and IC50) as well as structures of these complexes in PDBbind are integrated into a free web-based database (http://www.pdbbind-cn.org). Keywords: PDBbind database; CASF; Binding Affinity; Scoring Function; Benchmark References: [] Yan Li, Minyi Su, Zhihai Liu, Jie Li, Jie Liu, Li Han, Renxiao Wang *, Nature Protocols, 207, In press. [2] Zhihai Liu, Minyi Su, Li Han, Jie Liu, Qifan Yang, Yan Li*, and Renxiao Wang*, Accounts of Chemical Research, 207, 50 (2): 302-309. [3] Zhihai Liu, Yan Li, Li Han, Jie Li, Jie Liu, Zhixiong Zhao, Wei Nie, Yuchen Liu and Renxiao Wang, Bioinformatics, 205, 3 (3): 405-42. [4] Li, Yan; Liu, Zhihai; Li, Jie; Han, Li; Liu, Jie; Zhao, Zhi-Xiong; Wang, Renxiao *, J. Chem. Inf. Model. 204, 54, 700-76. [5] Li, Yan; Han, Li; Liu, Zhihai; Wang, Renxiao *, J. Chem. Inf. Model. 204, 54, 77-736. [6] Wang, R.; Fang, X.; Lu, Y.; Yang, C.-Y.; Wang, S., J. Med. Chem., 2005; 48(2); 4-49. [7] Wang, R.; Fang, X.; Lu, Y.; Wang, S., J. Med. Chem., 2004; 47(2); 2977-2980. 225

P--022 数据挖掘辅助化学实验条件优化设计卢凯亮, 张庆 2, 纪晓波 3, 陆文聪,3* 上海大学材料基因工程研究院,200444 2 上海大学材料科学与工程学院,200444 3 上海大学理学院化学系,200444 *Email: xuruhuan@i.shu.edu.cn 本工作运用遗传算法 - 支持向量回归 [] 筛选影响钴铝层状双金属氢氧化物 (Co-Al LDHs) 氟离子吸附容量的主要特征变量, 结果表明复合材料的钴元素的摩尔比 (Co%) 吸附剂的剂量 (M) 溶液的 ph 值 (ph) 溶液的氟离子浓度 (C) 是主要特征变量 [2] 利用上述特征变量构建支持向量回归模型, 留一法交叉验证的均方根误差和平均相对误差分别为 0.50 和 9.5%, 实验值和预报值的相关系数为 0.943 设计样本基于支持向量回归模型 (SVR) 预报的氟离子吸附容量与验证实验结果相一致 因此, 本工作所建立的支持向量回归模型有望在氟离子吸附容量预报工作中得到进一步的应用 Fig. Experimental versus predicted fluoride adsorption capacity for training data set (black, circle) and test dataset (red, square). 关键词 : 数据挖掘 ; 优化设计 ; 支持向量回归 ; 特征选择 参考文献 []Xiong, P.; Ji, X.; Zhao, X.; Lv, W.; Liu, T.; Lu, W. Chemometr Intell Lab. 205, 44:-6. [2]Zhao, X.; Zhang, L.; Xiong, P.; Ma, W.; Qian, N.; Lu, W. Micropor Mesopor Mat. 205, 20:9-98. 226

P--023 钠 - 葡糖共转运蛋白 2( SGLT2) 与其抑制剂的作用机理研究董利利, 冯睿蕊, 王冷, 许晔飞, 路慧哲,* 张建军,* 中国农业大学, 理学院应用化学系, 北京,0093 *Email: luhz@cau.edu.cn; 0600@cau.edu.cn 钠 - 葡糖共转运蛋白 2( SGLT2) 是一个治疗 II 型糖尿病的关键靶标, 在临床研究上具有重要意义 我们采用比较分子力场分析 ( CoMFA) 和比较分子相似因子分析 ( CoMSIA) 方法, 对 40 个 C- 糖苷类 SGLT2 抑制剂进行了三维定量构效关系 ( 3D-QSAR) 研究, 建立了交叉验证系数 ( r 2 cv) 分别为 0.646 和 0.577 的 CoMFA 模型和 CoMSIA 模型 在缺乏人源 SGLT2(h SGLT2) 晶体结构的情况下, 我们采用同源模建的方法, 并利用分子对接研究了 h SGLT2 和抑制剂的微观作用方式 随后 40ns 的动力学模拟进一步的探究了它们的动态结合机制, 结合自由能计算结果和 3D-QSAR 结果相一致, 都表明氢键 疏水和静电作用对抑制剂的结合起到了关键作用, 为进一步设计开发新型 2 型糖尿病抑制剂提供了理论依据 Fig. (A)3D contour plots of the CoMFA and CoMSIA. (B) Representation of the binding sites of homology hsglt2 and galactose. Fig.2 (A) binding modes of compound 40 in the active site of hsglt2 (B) RMSD changes of the hsglt2-40 complex during MD simulations of 40 ns 关键词 : 钠 - 葡糖共转运蛋白 2( SGLT2);II 型糖尿病 ; 同源模建 ; 动力学模拟 ; 三维定量构效关系 ( 3D-QSAR) 参考文献 [] Dong, L.; Feng, R.; Wang, L.; Xu, Y.; Lu*, H.; Zhang*, J.; J. Mol Model. ( unpublished). 227

P--024 Comparative analyses of structural features and scaffold diversity for purchasable compound libraries Jun Shang,2, Huiyong Sun 2, Hui Liu 2, Fu Chen 2, Sheng Tian 4, Peichen Pan 2, Dan Li 2, Dexin Kong,*, Tingjun Hou *,2,3 State Key Laboratory of Agricultural Microbiology and Agricultural Bioinformatics Key Laboratory of Hubei Province, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China. 2 College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 30058, China. 3 State Key Lab of CAD&CG, Zhejiang University, Hangzhou, Zhejiang 30058, China. 4 College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu 2502, China. *Email: Dexin Kong: dxkong@mail.hzau.edu.cn Tingjun Hou: tingjunhou@zju.edu.cn Large purchasable screening libraries of small molecules afforded by commercial vendors are indispensable sources for virtual screening (VS). Due to roaing molecular numbers, selecting an optimal screening library for a specific VS campaign is quite important to improve the success rates and avoid wasting resources in later experimental phases. Analysis of the structural features and molecular diversity for different screening libraries can provide valuable information to the decision making process when selecting screening libraries for VS. In this study, the structural features and scaffold diversity of eleven purchasable screening libraries and Traditional Chinese Medicine Compound Database (TCMCD) were analyzed and compared. Their scaffold diversity represented by the Murcko frameworks and Level scaffolds was characterized by the scaffold counts and cumulative scaffold frequency plots, and visualized by Tree Maps and SAR Maps. The analysis demonstrates that, based on the standardized subsets with similar molecular weight distributions, Chembridge, ChemicalBlock, Mucle, TCMCD and VitasM are more structurally diverse than the others. Compared with all purchasable screening libraries, TCMCD has the highest structural complexity indeed but more conservative molecular scaffolds. Moreover, we found that some representative scaffolds were important components of drug candidates against different drug targets, such as kinases and G protein-coupled receptors, and therefore the molecules containing pharmacologically important scaffolds found in screening libraries might be potential inhibitors against the relevant targets. This study may provide valuable perspective on which purchasable compound libraries are better for you to screen. Keywords: Scaffold Diversity; TCMCD; Scaffold Tree; Tree Map; SAR Map References: [] Shang J, Sun H-Y, Liu H, Chen F, Tian S, Pan P-C, Li D, Kong D-X, Hou T-J. Comparative analyses of structural features and scaffold diversity for purchasable compound libraries. J. Cheminform., 207, 9:25. 228

P--025 LDS 抑制剂设计与动力学研究佘柰, 马一鸣 2,, 赵媛,*, 河南大学天然药物与免疫工程重点实验室, 河南开封,475004 2 河南大学化学化工学院, 地址, 邮编 *Email: 4068586@qq.com LSD 是胺氧化酶家族 (MAO) 中的一员, 能特异性的脱去单甲基化和二甲基化的 H3K4 和 H3K9 位点上的甲基基团 [-2] 我们基于实验得到的苯环丙胺类系列 LSD 抑制剂, 采用分子对接 分子动力学模拟及 MM/GBSA 方法, 获取活性最优的化合物与 LSD 的结合模式 结合自由能及关键残基贡献 ; 并采用 Jarzynski Equality 方法获取该化合物逃离蛋白质的平均力势曲线, 对过程中的热动力学性质及关键残基进行探讨 此外, 本文根据该类抑制剂的结构特点, 建立了 3D-QSAR 模型, 采用 CoMFA 和 CoMSIA 方法分析影响抑制剂活性的结构特征, 并设计 22 个抑制剂, 利用分子对接方法, 根据结合模式及打分函数, 选取其中 3 个较优化合物作为研究对象, 并对它们进行长时间动力学模拟 通过 MM/GBSA 方法和拉伸分子动力学方法, 分别获得其结合自由能及释放过程相关性质, 并与实验中活性最好的化合物进行对比验证, 找出热动力学行为最优的潜在抑制剂 研究发现 Met332 - Gly336,Asn535-Asn540,Trp382 - His564 及 Asn806 - His 82 四段氨基酸残基对该类抑制剂结合起到关键作用,Thr65,Thr640,His642 等氨基酸在抑制剂释放过程中较为重要, 释放能垒约 5.2 kcal / mol, 主要来源于 Thr65 形成的氢键 52 号分子苯环位置对位增大基团且加入给电子基团设计出的抑制剂在活性方面有所改进, 并经分子对接及分子动力学模拟验证, 筛选出 3* 号化合物为较优潜在抑制剂 我们期望此项研究能够为未来 LSD 抑制剂的设计提供帮助 LSD - 抑制剂复合物 关键词 :LSD 抑制剂 ;3D-QSAR; 分子对接 ; 分子动力学模拟 ;SMD 参考文献 [] Whyte, Warren A., et al. "Enhancer decommissioning by LSD during embryonic stem cell differentiation." Nature 482.7384 (202): 22. [2] Bannister, Andrew J., and Tony Kouzarides. "Reversing histone methylation." Nature 436.7054 (2005): 03. 229

P--026 Understanding the structural and energetic basis of PD- and monoclonal antibodies bound to PD-L: a molecular modeling perspective Danfeng Shi, Shuangyan Zhou2, Xiaojun Yao,* State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, China 2 School of Pharmacy, Lanzhou University, Lanzhou 730000, China *Email: xjyao@lzu.edu.cn The inhibitors blocking the interaction between programmed cell death protein (PD-) and programmed death-ligand (PD-L) can activate the immune response of T cell and eliminate cancer cells. The crystallographic studies have provided structural insights of the interactive interfaces between PD-L and its protein ligands. However, the hotspot residues on PD-L as well as structural and energetic basis for different protein ligands still need to be further investigated. Molecular modeling methods including molecular dynamics simulation, per-residue free energy decomposition, virtual alanine scanning mutagenesis and residue-residue contact analysis were used to qualitatively and quantitatively analyze the interactions between PD-L and different protein ligands. The results of virtual alanine scanning mutagenesis suggest that Y56, Q66, M5, D22, Y23, R25 are the hotspot residues on PD-L. The residue-residue contact analysis further shows that PD- interact with PD-L mainly by F and G strands while monoclonal antibodies like avelumab and BMS-936559 mainly interact with PD-L by CDR2 and CDR3 loops of the heavy chain. A structurally similar β-hairpin peptide with 3 or 4 residues was extracted from each protein ligand and these β-hairpin peptides were found tightly binding to the putative hotspot residues on PD-L. This study recognizes the hotspot residues on PD-L and uncovers the common structural and energetic basis of different protein ligands binding to PD-L. These results will be valuable for the design of small molecule or peptide inhibitors targeting on PD-L. Fig. The hotspot residues on PD-L and the common structural and energetic basis of different protein ligands. Keywords: PD-L; PD-; monoclonal antibody; molecular dynamics simulation; virtual alanine scanning mutagenesis References: [] Zak, K.M.; Kitel, R. et al. Structure 205, 23: 234. [2] Pascolutti, R.;Sun, X. et al. Structure 206, 24: 79. 230

P--027 数据挖掘在钙钛矿光催化的应用石丽, 张庆 2, 卢凯亮 3, 陆文聪,3* 上海大学材料基因工程研究院,200444 2 上海大学材料科学与工程学院,200444 3 上海大学理学院化学系,200444 *Email: 25203684@qq.com 本工作运用遗传算法 - 支持向量回归 [] 筛选影响钙钛矿光催化性能的因素, 以 bandgap 为目标变量, 收集到 0 个特征变量, 通过变量筛选出 4 个特征变量, 有 A 位的离子半径 (Ra),B 位的离子半径 (Rb),B 位的原子序数 (Nb),A 位的电离能 (Ea) 利用上述特征变量构建支持向量回归模型, 留一法交叉验证的均方根误差为 0.603, 平均相对误差分别为 5.78%, 实验值和预报值的相关系数为 0.9847 通过原子参数, 能够预测钙钛矿的 bandgap, 进而快速预测钙钛矿材料的光催化性能 [2] 因此, 运用数据挖掘技术, 在光催化材料发现和应用方面有更好的前途 Fig. Experimental versus predicted perovskite bandgap for training data set (black, circle) and test dataset (green, square). 关键词 : 数据挖掘 ; 钙钛矿 ; 支持向量回归 ; 光催化性能 参考文献 []Xiong, P.; Ji, X.; Zhao, X.; Lv, W.; Liu, T.; Lu, W. Chemometr Intell Lab. 205, 44:-6. [2] Lu Wen-cong.;Ji Xiao-bo.;Li Min-jie.;Liu Liang.;Yue Bao-hua.;Zhang, Liang-miao.;Adv. in Manuf. 203, (2), 5-59. 23

P--028 完善评价蛋白 - 配体打分函数性能的 CASF 方法体系苏敏仪, 李嫣, 刘志海, 王任小,* 中国科学院上海有机化学研究所, 上海市徐汇区零陵路 345 号,200032 *Email: wangrx@sioc.ac.cn 亲合性打分函数由于其具有计算消耗小, 计算结果准确性尚可等优点而得到了广泛的应用 一个标准的评价体系可以帮助研究者客观了解打分函数的性能及其局限性, 为打分函数的发展奠定一个扎实的基础 本课题组致力于发展一个高质量的打分函数评价体系 CASF(comparative assessment of scoring functions), 目错误! 前已发布了两个版本 CASF-2007 错误! 未找到引用源 和 CASF-203 未找到引用源 - 错误! 未找到引用源 为进一步完善 CASF 评价体系, 我们 () 从 PDBbing-CN 数据库中严格地挑选 285 个蛋白 - 配体复合物 ( 含 57 个靶点 ), 每个靶点增加至 5 个不同结合水平的复合物 ;(2) 完善打分能力, 排序能力, 对接能力和筛选能力等四个评价指标, 增加统计检验衡量不可避免的抽样误差以及实验数据自身的测量误差 ;(3) 增加参与评价的打分函数, 涵盖了当前打分函数的四大分类, 使得我们的评价结果更加完整 Fig. Success rates of 32 scoring functions in the docking power test when the top one (red bars), the top two (green bars), or the top three (blue bars) best-scored ligand binding poses are considered to match the native binding pose. Here, scoring functions are ranked by their top success rates. A success prediction is counted if the RMSD of top-ranked pose is below a typical cutoff 2.0 Å. 关键词 : 打分函数 ; 性能评价 ; PDBbind 参考文献 [] Cheng, T.; Li, X.; Li, Y.; Liu, Z.; Wang, R. Comparative assessment of scoring functions on a diverse test set. J. Chem. Inf. Model. 2009, 49: 079 093. [2] Li, Y.; Liu, Z. H.; Han, L.; Li, J.; Liu, J.; Zhao, Z. X.; Li, C. K.; Wang, R. X. Comparative Assessment of Scoring Functions on an Updated Benchmark: I. Compilation of the Test Set. J. Chem. Inf. Model. 204, 54: 700 76. [3] Li, Y.; Han, L.; Liu, Z. H.; Wang, R. X. Comparative Assessment of Scoring Functions on an Updated Benchmark: II. Evaluation Methods and General Results. J. Chem. Inf. Model. 204, 54: 77 736. 232

P--029 快速结合效应介导的 crizotinib 手性异构体在 MTH 结合过程中的差异性孙慧涌, 侯廷军 * 浙江大学, 药学院, 杭州,30058 Email: tingjunhou@zju.edu.cn Crizotinib 作为最有效的抗肿瘤药物之一, 其在 MTH 介导的 RAS 依赖型肿瘤实验中依然成效显著 虽然不同的 crizotinib 手性异构体在 MTH 中的结合模式完全相同 (Nature 204, 508, 222-227), 然而这种治疗有效性仅体现在 S 型 crizotinib 中 ( 并非激酶靶点中通常使用的 R 型 crizotinib) 为了探究手性异构体在靶标结合中的差异性, 作者通过亚动力学模拟和势能面分解分析揭示了 (S)-crizotinib 和 (R)-crizotinib 在 MTH 中结合过程的差异性 有趣的是, 并非研究者通常所认为的诱导契合效应 ( 二级结合效应 ) 主导着药物与靶标结合的选择性与特异性 (Science 205, 347, 882-886), 快速结合过程 ( 一阶结合效应 ) 主导了不同手性 crizotinib 与 MTH 的结合 由于手性化合物与同一靶标结合时的结合模式通常相同 ( 即一般产生相近的诱导契合效应 ), 因此手性化合物的结合能力差异性可能更多的体现在药物 - 靶标结合的第一阶段, 即快速结合阶段 该工作可能为后续手性化合物的设计与筛选提供帮助 关键词 : 手性差异性分析, 自由能计算 参考文献 : [] Sun, H.; Chen, P.; Li, D.; Li, Y.; Hou, T. Directly Binding Rather Than Induced-Fit Dominated Binding Affinity Difference in (S) and (R)-Crizotinib Bound MTH. J. Chem. Theory Comput. 206, 2, 85-860 233

P--030 Different multi-label strategies for the prediction of endocrine disrupting activity of environmental compounds LiXia Sun, Yun Tang,* Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 30 Meilong Road, Shanghai, 200237 Email: ytang234@ecust.edu.cn Endocrine disrupting (ED) have become a serious public health problem. Endocrine disrupting chemicals (EDCs) mainly work by interacting with distinct hormone receptors. The complex biology of ED means that no single computational prediction is sufficient to identify chemicals with EDC activity. Current in silico models are generally specific to only one mechanism of action. However, some chemicals can act through multiple mechanisms, necessitating the employment of a model to cover a comprehensive range of potential modes of ED and reduce the risks of false negatives. In this endeavor, multi-label approaches which can predict multiple labels for a chemical at the same time were utilized to provide a fuller picture of endocrine disrupting characteristics. And diverse data sets from Tox2 involving multiple well-studied endocrine signaling pathways were curated for model training and evaluation, which includes six nuclear receptor targets - estrogen receptor (ER), androgen receptor (AR), thyroid receptor (TR), glucocorticoid receptor (GR), peroxisome proliferator-activated receptor γ (PPARγ), Retinoid X receptor (RXR), and one hormone metabolism enzyme - aromatase. Considering that traditional multi-label learning methods are limited by the data available for all the targets at the same time, we designed three experimental protocols: first, constructing single-label models with all the data available for each target separately and then combining all the best single-label models to get a multi-label prediction; second, only the multi-label data was trained with the multi-label algorithms; last, chemicals with activity call for at least 6 targets were employed and the missing one is held as non-binder, and then models were trained with the new generated multi-label data. To compare the models quality, a multi-label test set of 75 chemicals with experimental activity classification for all the 7 targets were used. Four fingerprints (FP, MACCS, ExtFP, Pubchem) combined with four machine learning algorithms namely k-nearest Neighbor (knn), Random Forest (RF), Artificial Neural Net (ANN) and Support Vector Machine (SVM) were used to construct single-label models. For the latter two multi-label strategies, four multi-label classification frameworks - Binary Relevance (BR), Classification Chain (CC), Pruned Sets (PS), and Random k-labelsets (RAkEL) were used with RF and SVM as the base classifiers. And the best models were PS-RF-ExtFP and PS-RF-MACCS respectively. Obviously, despite less training data, multi-label models based on multi-label algorithms outperformed the single-label ones, which manifests that multi-label learning approaches can benefit the prediction of ED activity and there are some correlations between these targets we studied. Fig. Different multi-label classification schemes. Keywords: Endocrine disrupting chemicals (EDCs); Tox2; multi-label models 234

P--03 ADMETlab: 一个系统的 ADMET 性质在线预测平台 王柠柠, 董界, 曹东升 中南大学湘雅药学院, 长沙市岳麓区桐梓坡路 72 号,40003 *Email: oriental-cds@63.com 当代药物研发失败的主要原因是候选化合物在其效用及安全性方面的不足, 这些不足在一定程度上与化合物本身的吸收 分布 代谢 排泄及各种毒性 (ADMET) 相关 因此, 在药物研发的初期快速有效地对候选化合物进行系统的 ADMET 性质评估是十分必要的 本研究中, 我们基于一个全面收集的 由 288967 个条目组成的数据库构建了一个系统的 ADMET 性质在线预测平台 该平台主要包括四个功能模板 :6 种类药性分析方法 ;3 个预测 ADMET 性质的 QSAR 模型 ; 系统 ADMET 评估及相似性搜索 我们相信该预测平台有望通过早期 ADMET 性质的系统评估及对候选化合物的结构优化来推进未来药物研发的整个流程 关键词 :ADMET; 预测平台 ;QSAR 模型 ; 类药性分析 ; 相似性搜索 参考文献 [] Wang N N, Dong J, Deng Y H, et al. J Chem Inf Model, 206, 56(4): 763. [2] Wang N N, Huang C, Dong J, et al. RSC Adv, 207, 7(3): 9007. 235

P--032 Prediction of Binding Modes and Binding Affinities of Propanidid and AZD-3043 with the GABAA Receptor by Docking and ONIOM Calculations Shanshan Wang, Xi Li, Qingzhu Liu, Xueyu Zhao, Jianguo Lin, Ling Qiu * Key Laboratory of Nuclear Medicine, Ministry of Health & Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, 24063 * E-mail: qiuling@jsinm.org. Propanidid is an intravenous anesthetic with transient action and rapid recovery features, but it is clinically unacceptable due to its side effects. AZD-3043, an analog of propanidid with the methoxy group substituted by the ethoxy group, has become the focus of recent development efforts. Although propanidid and AZD3043 are known to act by potentiatingthe γ-aminobutyric acid type A receptors (GABAARs), their action sites and binding modes in the recognition of target proteins still remain unclear. In this study, molecular docking and ONIOM calculations were performed to explore the possible binding sites and binding modes of propanidid and AZD-3043 with the GABAAR. The predicted active region located in the transmembrane (TM) domain of GABAAR was identified as the most favorable binding site for propanidid and AZD-3043, with the highest docking score (-39.69 kcal/mol and -39.44 kcal/mol, respectively) and the largest binding energy (-88.478 kcal/mol and -78.439 kcal/mol, respectively). The important role of amino acids Asp245, Asp424, Asp425, Arg428, Phe307 and Ser308 in determining the binding modes of propanidid or AZD-3043 with GABAAR was revealed. The detailed molecular interactions between propanidid and AZD-3043 and the GABAAR were revealed for the first time. This could improve our understanding of the action mechanism of general anesthetics and will be helpful for design of more potential lead-like molecules. Fig. Structures of the ligand (Propanidid and AZD-3043) and the GABAA receptor. Keywords: propanidid; AZD-3043; GABAA receptor; molecular docking; ONIOM calculation References: [] Miller, P. S.; Aricescu, A. R. Nature. 204, 52: 270. [2] Franks, N. P. Anesthesiology. 205, 22: 787. 236

P--033 Comprehensive evaluation of ten docking programs on a diverse set of protein-ligand complexes: prediction accuracy of sampling power and scoring power Zhe Wang, Tingjun Hou,2,* College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 30058 2 State Key Lab of CAD&CG, Zhejiang University, Hangzhou, 30058 *Email: tingjunhou@zju.edu.cn As one of the most popular computational approaches in modern structure-based drug design, molecular docking can be used not only to identify the correct conformation of a ligand within the target binding pocket but also to estimate the strength of the interaction between a target and a ligand. Nowadays, as a variety of docking programs are available for the scientific community, a comprehensive understanding of the advantages and limitations of each docking program is fundamentally important to conduct more reasonable docking studies and docking-based virtual screening. In the present study, based on an extensive dataset of 2002 protein ligand complexes from the PDBbind database (version 204), the performance of ten docking programs, including five commercial programs (LigandFit, Glide, GOLD, MOE Dock, and Surflex-Dock) and five academic programs (AutoDock, AutoDock Vina, LeDock, rdock, and UCSF DOCK), was systematically evaluated by examining the accuracies of binding pose prediction (sampling power) and binding affinity estimation (scoring power). Our results showed that GOLD and LeDock had the best sampling power (GOLD: 59.8% accuracy for the top scored poses; LeDock: 80.8% accuracy for the best poses) and AutoDock Vina had the best scoring power (rp/rs of 0.564/0.580 and 0.569/0.584 for the top scored poses and best poses), suggesting that the commercial programs did not show the expected better performance than the academic ones. Overall, the ligand binding poses could be identified in most cases by the evaluated docking programs but the ranks of the binding affinities for the entire dataset could not be well predicted by most docking programs. However, for some types of protein families, relatively high linear correlations between docking scores and experimental binding affinities could be achieved. To our knowledge, this study has been the most extensive evaluation of popular molecular docking programs in the last five years. It is expected that our work can offer useful information for the successful application of these docking tools to different requirements and targets. Fig. The sampling power and scoring power of ten docking programs. Keywords: molecular docking; pose sampling; scoring function; virtual screening References: [] Wang Z., Sun H., Yao X., Li D., Xu L., Li Y., Tian S., Hou T. Phys. Chem. Chem. Phys., 206, 8:2964-2975 237

P--034 Support Vector Regression Assisted Predictions of Néel temperature of ABO3 perovskites LinhuiXiao, Qing Zhang 2, Xiao Xu, Xiaobo Ji, Wencong Lu, * Department of Chemistry, College of Sciences, Shanghai University, Shanghai, 200444 2 College of Materials Science and Engineering, Shanghai University, Shanghai, 200444 *E-mail: wclu@shu.edu.cn Abstract: Efficient and effective prediction of the Néel temperaturetn(k) is of great important to material design of ABO3 type perovskite with the space group pbnm. In this work, support vector regression [,2] was applied to represent the relationship between the Néel temperaturetn(k)and structural parameters of the ABO3 type perovskite. The GA(genetic algorithm)-svr(support vector regression) method was used to select the main descriptors in modeling. Feature selection shows that four molecular parameters including the ionic radius of the position B metal element(r b), critical radius(r c), the ratio of the number of valence electrons and its ionic radius for position B metal element(zb/rb) and electron affinity of position B metal element(ab) are important to the model building. A nonlinear relation between the Néel temperaturetn(k) and above four descriptors is constructed on basis of radial basis function. The result of LOOCV test and an external validation test suggest that the QSPR model has great generalization ability. Therefore, the method can be used to predict the Néel temperaturetn(k) in computer aided molecular design of perovskite material. Fig.. Experimental T N versus predicted T N of perovskite sample by SVR in LOOCV test (white, circle) and the test set (red, solid circle). Keywords: Perovskite; Néel temperaturetn(k);support Vector Regression; References: []Vapnik Vladimir N, The Nature of statistical Learning Theory. Berlin, Springer,995 [2] Wencong Lu, XiaoboJi, Minjie Li, Liang Liu.Advances in Manufacturing. 203, (2):5 59 238

P--035 Statistical Analysis, Investigation, and Prediction of the Water Positions in the Binding Sites of Proteins Wei Xiao,2, Honglin Li,2,* School of Information Science and Engineering, East China University of Science and Technology, 30 Meilong Road, Shanghai, 200237, China 2 Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 30 Meilong Road, Shanghai 200237, China *Email: hlli@ecust.edu.cn ABSTRACT Water molecules play a crucial role in biomolecular associations by mediating a hydrogen bond network or filling spaces with van der Waals interactions. Although current drug design technologies have taken water molecule interactions into account, their applications are still limited to their reliance on either excessive computer resources or a particular potential energy model. Here, we introduce a statistical method that is based on experimentally-determined water molecules in the binding sites of high-resolution X-ray crystal structures to predict the potential hydration sites in the binding sites of crystal structures of interest. By clustering and analyzing the various interaction patterns of water molecules in the training data set, we derived a tetrahedron-water-cluster model based on a series of residue group triplets that form feature triangles of different shapes. In the tetrahedral-water-cluster model, a triplet of three polar atoms in the residue group triplet acts as the vertices of the bottom triangle of the tetrahedron, and the water molecule that interacts with these three polar atoms is set as the top vertex of the tetrahedron. By comparing the shapes of the bottom triangles in the training data set with the shape of the triangle in the residue group triplets in the crystal structure of interest, we can identify the bottom triangle that is most similar to the one in the residue group triplet of the crystal structure of interest. According to the tetrahedron-water-cluster model, the hydration site for the residue group triplet in the crystal structure of interest can be predicted based on the height of the tetrahedron that has the most similar bottom triangle in the training data set. A test set containing 93 crystal structures was used to evaluate model performance, and extensive comparison with the recently published program Dowser++ revealed that our model is at least as good at providing an accurate set of the potential hydration sites in crystal structures of interest. Keywords: water molecules; the tetrahedral-water-cluster model; predict; hydration References: [] Zheng, M.; Li, Y.; Xiong, B.; Jiang, H.; Shen, J. Water PMF for predicting the properties of water molecules in protein binding site. J. Comput. Chem. 203, 34, 583-592. [2] Lu, Y.; Wang, R.; Yang, C. Y.; Wang, S. Analysis of ligand-bound water molecules in high-resolution crystal structures of protein-ligand complexes. J. Chem. Inf. Model. 2007, 47, 668-675. [3] Corbeil, C. R.; Moitessier, N. Docking Ligands into Flexible and Solvated Macromolecules. 3. Impact of Input Ligand Conformation, Protein Flexibility, and Water Molecules on the Accuracy of Docking Programs. J. Chem. Inf. Model. 2009, 49, 997-009. 239

P--036 数据挖掘在氟橡胶生产装置工艺优化中的应用徐潇, 张庆 2, 卢凯亮 3, 陆文聪,3* 上海大学理学院化学系,200444 2 上海大学材料科学与工程学院,200444 3 上海大学材料基因工程研究院,200444 企业产品质量和工艺波动数据蕴含了生产规律性, 如何利用数据挖掘方法总结生产波动数据, 用以产品质量的优化控制, 这是企业挖潜增效的有效技术方法 3 收集了氟橡胶(FKM) 生产装置有关工艺数据, 利用统计分析和 Fisher 判别矢量法等数据挖掘方法分析了 FKM 产品的门尼黏度与其生产工艺间的关系, 得到了 FKM 产品的生产工艺优化方案, 并在生产装置上进行实施, 使得产品的门尼黏度在 36~45 的生产合格比例由 53% 提高到 85%, 大幅增加了 FKM 产品的门尼黏度合格率, 提高了企业的经济效益 4 Figure Menny viscosity distribution Figure 2 Menny viscosity distribution before optimization after optimization 关键词 : 氟橡胶 ; 门尼黏度 ; 数据挖掘 ; 工艺优化参考文献 [] 陆文聪, 李国正, 刘亮, 等. 化学数据挖掘方法与应用 [M]. 第一版. 北京 : 化学工出版社业, 20: -5. [2] 李鹏, 郑晓军, 明梁, 等. 大数据技术在催化裂化装置运行分析中的应用 [J]. 化工进展, 206, 35 (3): 665-670. [3] Kusiak A, Wei X. Prediction of methane production in wastewater treatment facility: a data-mining approach[j]. Annals of Operations Research, 204, 26(): 7-8. [4] 邬一凡, 黄巍, 徐京生. 国内外氟橡胶生产消费现状及发展趋势 [J]. 化工新型材料, 203, 4(3): -5. 240

P--037 Deep Learning Based Regression and Multi-class Models for Acute Oral Toxicity Prediction with Automatic Chemical Feature Extraction Youjun Xu, Jianfeng Pei,*, Luhua Lai,2,* Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 0087, China 2 Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing 0087, China *Email: yjxu@pku.edu.cn Median lethal death, LD50, is a general indicator of compound acute oral toxicity (AOT). Various in silico methods were developed for AOT prediction to reduce costs and time. In this study, we developed an improved molecular graph encoding convolutional neural networks (MGE-CNN) architecture to construct three types of high-quality AOT models: regression model (deepaot-r), multi-classification model (deepaot-c) and multi-task (deepaot-cr). These predictive models highly outperformed previously reported models. For the two external data sets containing 673 (test set I) and 375 (test set II) compounds, the R2 and mean absolute error (MAE) of deepaot-r on the test set I were 0.864 and 0.95, and the prediction accuracy of deepaot-c was 95.5% and 96.3% on the test set I and II, respectively. The two external prediction accuracy of deepaot-cr is 95.0% and 94.%, while the R2 and MAE are 0.86 and 0.204 for test set I, respectively. We then performed forward and backward exploration of deepaot models for deep fingerprints, which could support shallow machine learning methods more efficiently than traditional fingerprints or descriptors. We further performed automatic feature learning, a key essence of deep learning, to map the corresponding activation values into fragment space and derive AOT-related chemical substructures by reverse mining of the features. Our deep learning architecture for AOT is generally applicable in predicting and exploring other toxicity or property endpoints of chemical compounds. The two deepaot models are freely available at http://repharma.pku.edu.cn/dlaot/dlaothome.php. Fig. MGE-CNN architecture for AOT prediction. Keywords: Acute oral toxicity, convolution neural network, deep fingerprints, structural fragments References: [] Xu, Y.; Pei, J.; Lai, L. J. Chem. Inf. Model. 207. In revision. 24

P--038 Discovery of LspA Inhibitors as Novel Antibacterial Agents: Virtual Screening, Synthesis and Biological Evaluation Wenjie Xue, Jie Xia *, Bo Feng, Xiang Simon Wang 2, Song Wu * State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 00050, China; 2 Molecular Modeling and Drug Discovery Core Laboratory for District of Columbia Center for AIDS Research (DC CFAR), Department of Pharmaceutical Sciences, College of Pharmacy, Howard University, Washington, DC 20059, U.S.A. *Email: S.W. (ws@imm.ac.cn) or J.X. (jiexia@imm.ac.cn) The emergence and spread of antibiotic resistance represent a severe global issue. New drug targets and novel lead compounds that exempt from cross-resistance to existing drugs are urgently needed. LspA, a key enzyme involved in posttranslational processing of bacterial lipoprotein, looms as one of the new targets for antibacterial agents discovery. So far, only one class of LspA inhibitors (LspAIs), i.e. globomycin and its derivatives, has been reported as active against a panel of bacteria. Owing to the lack of potency, however, no significant advance was made for this class of LspAIs. Recently, the crystal structure of LspA bound to globomycin was solved, which established the foundation for structure-based drug design (SBDD). In this study, we developed a virtual screening (VS) pipeline based on cocrystal structure of LspA and applied it to a screening campaign for LspAIs as antibacterial agents. With this powerful pipeline, we discovered a novel hit compound from Specs chemical library. Based on its new scaffold, we further designed and synthesized 35 derivatives, of which 9 compounds showed potent inhibitory effects on Methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria. Because of the promising outcome, we will perform thorough SAR study as well as evaluation of lead compounds for their anti-mrsa activity, cytotoxicity and pharmacokinetic properties in the future. Keywords: antibacterial inhibitor, LspA, virtual screening, lead optimization, MRSA References: [] Hiramatsu, K.. Lancet. Infect. Dis. 200, : 47. [2] Marty, F. M.; Yeh, W. W.; Wennersten, C.B.; et al. J. Clini. Microbiol. 2006, 44: 595. [3] Endimiani, A.; Blackford, M.; Dasenbrook, E.C.; et al. Antimicrob. Agents Chemother. 20, 55: 684.. [4] Antonov, N. K.; Garzon, M. C.; Morel, K.D.; et al. Antimicrob. Agents Chemother. 205, 59: 3350. [5] Vogeley, L.; Arnaout, T. E; Bailey, J; et al. Science. 206, 35: 876. 242

P--039 OrangeModeling a tool for machine learning based quantitative structure-property relationship modeling Hongbin Yang, Yun Tang * Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 30 Meilong Road, Shanghai, 200237 Email: ytang234@ecust.edu.cn Machine learning methods for constructing quantitative structure-activity relationship (QSAR) or quantitative structure-property relationship (QSPR) models were widely applied in drug discovery, environmental conservation, and industry chemical supervision. Its high accuracy and less requirement of additional information make it possible to replace conventional in vivo and in vitro assays. Here, we share a tool we developed that is based on the machine learning methods driven by Orange and the fingerprints calculated by PaDEL-Descriptor. The protocol we used is widely applied in toxicity classification and prediction of drug-target interaction. Different from the previous studies, with this tool, the researchers need not repetitively model with different fingerprints and machine learning methods, or struggle with different platforms. Hyper-parameter optimization becomes more convenient as well. OrangeModeling supports nine fingerprint types calculated by PaDEL-Descriptor, i.e. CDK fingerprint, CDK extended fingerprint, Estate fingerprint, CDK graph only fingerprint, MACCS fingerprint, Pubchem fingerprint, Substructure fingerprint, Klekota-Roth fingerprint, and 2D atom pairs. Splice of these fingerprints is allowed for custom feature selection and combination. Six common machine learning methods are supported, i.e. Naïve Bayes (NB), classification tree (CT), random forest (RF), artificial neural network (ANN), k-nearest neighbors (knn), and support vector machine (SVM). The number of trees in RF, the number of hidden nodes in ANN, the k in knn, and the C and gamma in SVM are preset as hyper-parameters to be optimized. The kernel of SVM is radial basis function. SARpy is embedded in OrangeModeling to calculate the frequent substructures that occur in the particular dataset during modeling, which is helpful for regularization of industry chemicals and for avoiding potential risk of toxicity in drug discovery. All the results including the performance of the models and the frequent substructures will be output as a report to a pdf file. Additionally, we used this tool to model for different datasets and endpoints, including the toxicity classification such as oral acute toxicity, aquatic toxicity, bioactivity such as CYP inhibition, and some pharmacokinetics activity prediction (e.g. P-glucose protein combination), etc. The statistics results of the model performance with different parameters can help us exploit how to make an appropriate QSPR model. Fig. Workflow of OrangeModeling Fig.2 The Graphical user interface of OrangeModeling Keywords: Cheminformatics; classification model; machine learning; software 243

P--040 探讨评价打分函数中的统计问题杨启帆, 王任小,* 中国科学院上海有机化学研究所, 上海市零陵路 345 号,200032 *Email: wangrx@sioc.ac.cn 亲合性打分函数 (Scoring function) 是一类计算蛋白 - 配体亲合性的方法 相关系数 R 则是评价打分函数的一个重要的指标 在评价打分函数时, 用于计算相关系数的测试集只有一个, 因而计算的相关系数是 相倚的 (correlated) 目前已提出多个比较相倚相关系数的检验统计量 :Meng: ; Carlson: 等 本工作主要对 Carlson 检验统计量 () 和 Meng 检验统计量 (2) 的合理性进行研究, 并探讨了测试集的大小与统计效力和显著性水平的关系 实验结果表明, Carlson 检验统计量不能作为比较相依相关系数的方法, 而 Meng 检验统计量可以用来比较相倚相关系数 此外, 相倚关系数是一个重要参数, 随着相倚相关系数的下降, 测试集所需样本量急剧上升 相倚相关系数间差值越小, 所需要的测试集样本数越多 如图 - 所示 综上,Meng 检验统计量可以作为一种可靠的假设检验的方法应用于比较不同打分函数产生的相倚相关系数 应用 PDBbind 核心集作为测试集比较相关系数差值较大 相倚相关系数较大的一组相倚相关系数, 都可以得到较为良好的显著性水平和统计效力 关键词 : 打分函数 ; 样本数 ; 测试集 Fig. Required sample size of data set (one-tailed) ; ; 参考文献 [] Li, Y.; Han, L.; Liu, Z. H.; Wang, R. X. Journal of Chemical Information and Modeling 204, 54(6): 77-736. [2] Carlson, H. A. Journal of Chemical Information and Modeling 203, 53(8): 837-84. [3] Meng, X. L.; Rosenthal, R.; Rubin, D. B. Psychol. Bull. 992, (): 72-75. 244

P-2-00 拉曼光谱成像结合多元曲线分辨测定紫外线对不同防护条件下的皮肤损伤付宏, 张欣, 张卓勇 * 首都师范大学化学系, 北京市海淀区西三环北路 05 号,00048 *Email: gusto2008@vip.sina.com 拉曼光谱技术 (Raman spectroscopy technique) 是一种非破坏性的指纹成像技术, 因不需要样品前处理, 具有快速 无损检测的优点, 采用表面增强处理后能单分子水平获取物质的结构和组成信息, 适用于对生物体系的研究 本文基于拉曼光谱, 分别测定了裸鼠的表面和深度拉曼成像 在动物模型中, 将 30 只 BALA/c 雌性裸鼠分为 6 组, 每组 5 只, 分别涂抹物理防晒剂 TiO2, 化学防晒剂二甲苯酮 水杨酸异辛酯, 生物防晒剂辅酶 Q0 三大不同类型的防晒剂后, 进行紫外损伤实验, 并分析了裸鼠皮肤的变化情况 将不同裸鼠数据展开并合并成增广矩阵后, 采用多元曲线分辨交替最小二乘法 (Multivariate Curve Resolution-Alternating Least Squares, MCR-ALS) [4] 解析得到了皮肤中不同主成分拉曼纯光谱, 及其对应的各个主成分不同的浓度分布图 通过各主成分浓度变化趋势能够比较不同防晒剂的处理效果, 以及紫外线照射后皮肤损伤程度 对照组可作为空白实验数据施加选择性约束, 并获得相应的无扭曲模糊的分析结果 结果表明本文提出的建模方法可以作为一种皮肤损伤的测定方法, 同时也可以辅助不同试剂对皮肤损伤保护的测试研究 关键词 : 拉曼光谱 ; 皮肤 ; 防晒剂 ; 化学计量学 ; 多元曲线分辨 参考文献 []Murphy,Michael J. Molecular Diagnostics in Dermatology and Dermatopathology. 20,4-48. [2]Fan M; Andrade G F S; Brolo A G. Analytica Chimica Acta. 20, 693(): 7-25. [3]Zhang D; Wang P; Slipchenko M N, et al. Analytical Chemistry. 202, 85(): 98-06. [4]Felten, J.; Hall, H.; Jaumot, J.; Tauler, R.; De Juan, A. Nature Protocols. 205, 0(2): 27-240. [5]Yan W; Liu H; Deng X, et al. Lasers in Medical Science. 207, 32(5): 3-4. [6] 李莉莉, 赵丽娇, 钟儒刚. 光谱学与光谱分析, 202, 32(9):2422-2426 [7] 吴海游, 梁美婷, 邱楚群. 中国皮肤性病学杂志, 207, 3(4): 365-368 * 北京市科技创新平台项目 (75303900) 资助 245

P-2-002 Structure-based drug design of non-atp competitive small molecule inhibitor of Plk to treat cancer Jian Gao *, Weimin Qiu, Jiahao Xu, Wen Yang, Han Chen, Jie Mou Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 22004, Jiangsu, China *Email: gaojian@xzhmu.edu.cn Elevated expression of polo-like kinase (Plk) has been reported in a wide spectrum of cancers in humans, and inhibition of Plk activity results in mitotic arrest and apoptosis [-5]. We report here on diverse small molecule inhibitors with excellent anticancer activities designed based on high-throughput virtual screening (HTVS) study using the crystal structure of polo-like domain (PBD) of PLK. The compound M4076_0046 exhibited potent anticancer activities against Hela, MCF-7, and BT549 cell lines with IC50 of 8.38, 8.52, and 7.36 μm, respectively. Molecular docking studies suggested that M4076_0046 could interact with PLK by several conserved hydrogen bonds and hydrophobic interactions. The pharmacokinetic and toxicity properties predicted by the OSIRIS property exporer showed that M4076_0046 had a high drug score with no risk of toxicity. Thus, M4076_0046 might represent a promising lead compound for further development of novel anticancer drugs. Keywords: High-throughput virtual screening; polo-like kinase ; polo-box domain; anticancer References: [] Qin, T.; Chen, F.; Zhuo, X.; Guo, X.; Yun, T.; Liu, Y.; Zhang, C.; Lai, L., Discovery of Novel Polo-Like Kinase Polo-Box Domain Inhibitors to Induce Mitotic Arrest in Tumor Cells, J. Med. Chem. 206, 59: 7089-7096. [2] Normandin, K.; Lavallée, J.-F.; Futter, M.; Beautrait, A.; Duchaine, J.; Guiral, S.; Marinier, A.; Archambault, V., Identification of Polo-Like Kinase Interaction Inhibitors Using a Novel Cell-Based Assay, 206, 6: 3758. [3] Liu, Z.; Sun, Q.; Wang, X., Plk, a Potential Target for Cancer Therapy, Transl. Oncol. 207, 0: 22-32. [4] Yun, T.; Qin, T.; Liu, Y.; Lai, L., Identification of Acylthiourea Derivatives as Potent Plk Pbd Inhibitors, Eur. J. Med. Chem. 206, 24: 229-236. [5] Kumar, S.; Kim, J., Plk- Targeted Inhibitors and Their Potential against Tumorigenesis, BioMed Research International 205, 5: 2. 246

P-2-003 Theoretical Insights into Polymorphic Co-crystal of 5 Fluorouracil and 4-Hydroxybenzoic acid : Stability and Solubility Wei Gao, Xia-Lin Dai 2, Jia-Mei Chen 2,* School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, China, 50006 2 School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China, 50006 *Email: chenjm37@mail.sysu.edu.cn 5-Fluorouracil (5-Fu) is used as active pharmaceutical ingredients in treatment cancer, with moderate aqueous solubility and low permeability. To improve its bioavailability, co-crystals offer an effective tool toward fine-tuned balance between stability, solubility and permeability. As only one example of polymorphic co-crystal concerning 5-Fu, two crystal forms (I and II) of 5-Fu and 4-Hydroxybenzoic acid (4-HBA) are relevant in technological and scientific applications. However, the deficiencies of theoretical insights limit its co-crystal design strategies. In this paper, depending on different DFT approaches including vdw effects, the calculating lattice energy confirms substantially that the form I are more stable. From these structures, we clarify that how various intermolecular interactions occurring in two polymorphs work together to stabilize supramolecular assemblies by electronic density analysis. The aqueous solubility ratio of polymorphs is predicted from calculating thermal data with the Hoffman model expanded to co-crystal system, which reach well agreement with our further experiment. Meanwhile, in contrast to crystal solid, the atomistic pictures of how 5-Fu, 4-HBA and water interplay in aqueous solution are charactered by performing molecular dynamics simulations. Our attempts are believed to provide new insights into title crystals. Keywords: polymorphic co-crystal;stability and Solubility;5 Fluorouracil and 4-Hydroxybenzoic acid References: [] Li, S.; Chen, J.M; Lu, T.B. CrystEngComm. 204, 28: 6450. [2] Dai, X.L.; Li, S.; Chen, J.M; Lu, T.B. Cryst. Growth Des. 206, 6: 4430. [3] Hamad, S.; Moon, C.; Catlow, C. R. A.; Hulme, A. T.; Price, S. L. J. Phys. Chem. B. 2006, 0: 3323. [4] Karamertzanis, P. G.; Raiteri, P.; Parrinello, M.; Leslie, M.; Price, S. L. J. Phys. Chem. B. 2008, 2: 4298. 247

P-2-004 拉曼光谱成像技术结合化学计量学判别宫颈癌组织石蜡切片李颜, 张欣, 张卓勇 * 首都师范大学, 北京市海淀区西三环北路 05 号,00048 *Email: gusto2008@vip.sina.com 宫颈癌是一种严重威胁女性身体健康的恶性肿瘤, 其原位癌高发年龄为 30~35 岁, 浸润癌为 45~55 岁, 近年来其发病率有年轻化的趋势 目前, 宫颈癌检测样本大多为新鲜组织, 冰冻切片或者病理切片脱蜡, 医学常用诊断方法为肉眼观察 细胞学检测 HPV 检测与荧光镜检查等, 这些方法有较高的准确性, 时效性高, 但是操作复杂, 样品需一定保存条件, 重复性低, 所以迫切需要一种稳定的检测样本和无损的快速检测方法对宫颈癌的早期诊断和病理研究提供帮助 本文以宫颈癌组织为研究对象, 通过高光谱拉曼成像技术同时分析了宫颈癌癌症组织 宫颈炎症组织和正常组织的石蜡病理切片, 试图从组织病理切片中提取出组织和代谢成分信息 我们通过收集 22 条不同切片未知的拉曼光谱和 0 个切片拉曼高光谱成像, 建立了拉曼光谱对肿瘤组织的判别模型 偏最小二乘判别分析 (PLS-DA) 和主成分分析 (PCA) 结果表明对正常宫颈组织 宫颈上皮内瘤变 Ⅱ-Ⅲ 级 (CINⅡ-Ⅲ) 组织和宫颈癌组织分类准确率达到 00% 尽管组织病理切片中有严重的石蜡干扰, 正常宫颈组织 宫颈上皮内瘤变 Ⅱ-Ⅲ 级 (CINⅡ-Ⅲ) 组织和宫颈癌组织在分子指纹信息中仍有明显差别 宫颈组织拉曼高光谱成像结合多元曲线分辨 (MCR) 方法获得了数据中主成分纯光谱及其对应的成分浓度分布, 结果表明宫颈组织纯光谱含有丰富的生物信息, 病理切片的浓度分布也很好的吻合 本研究可以从宫颈组织病理切片中提取出新鲜宫颈组织信息, 为充分利用现有医疗和病理资源, 实现病理组织精准诊断和治疗提供了依据 关键词 : 拉曼光谱 ; 宫颈癌 ; 偏最小二乘 ; 多元曲线分辨 ; 拉曼成像 参考文献 [] Krishna, C. M.; Prathima, N. B.; Malini, R.; Vadhiraja, B. M. Vibrational Spectroscopy. 2006, 4: 36. [2] Krafft, C.; Steiner, G.; Beleites, C.; Salzer, R. J. Biophotonics. 2009, 2: 3. [3] Chylińska, M.; Szymańska-Chargot, M.; Zdunek, A. Plant Methods. 204, 0: 4. [4] Tfayli, A.; Piot, O.; Durlach, A.; Bernard, P. Biochimica et Biophysica Acta. 2005, 724: 262. [5] Shepherd, J. H. Best Practice & Research Clinical Obstetrics and Gynaecology. 202, 26: 293. 248

P-2-005 集成机器学习算法在癌症基因筛选及预后预测中的应用梁羽, 贺莉 2, 谢凡凡, 郝颖异, 李梦龙, 文志宁,* 四川大学化学学院, 成都市一环路南一段 24 号, 邮编 :60065 2 农业部沼气科学研究所, 成都市人民南路四段十三号, 邮编 :6004 *Email: w_zhining@63.com 单一机器学习算法已广泛应用于癌症预后的预测中, 但由于功能相似的基因之间存在冗余信息, 使得这些方法在进行特征筛选时容易忽略一些与疾病相关的基因 为了能得到相对更稳定模型及更全面的癌症相关基因集, 我们尝试了集成机器学习算法 该方法不仅可将多个机器学习方法集成在一起, 通过投票的方式对最终结果进行预测, 还可整合多个检测平台的数据, 如 mrna 测序平台 mirna 测序平台等, 利用不同平台从不同角度对同一样本的 表征, 实现对样本更为准确的分类 研究中, 针对 4 类肿瘤数据, 我们分别采用 5 种变量选择方法来分别对 mrna 和 mirna 两种测序平台进行变量的筛选以及利用 7 类建模方法, 总计建立了 980 个单一预测模型, 分别对各数据集中的病人预后指标进行预测 此外, 同时对比利用投票的方式将 7 类建模方法进行集成后的预测结果 研究结果表明, 对于癌症预后的预测, 我们提出来的集成学习算法比单一的机器学习算法更可靠, 并且我们的算法可以提供更全面 更完整的筛选出癌症相关的基因, 从而可以更好地促进癌症机制的探索和潜在的药物靶标的识别 由于该工作仅在探索集成机器学习算法的优势, 因此在预测时, 并没有加入任何关于癌症基因的先验知识, 如在实际应用中, 根据先验知识对癌症基因进行预筛选, 应能获得更准确的预测结果 关键词 : 癌症相关基因 ; 集成机器学习算法 ; 预测 ; 分类 参考文献 [] Jing, R., et al., Int. J. Genomics, 207. Under review. [2] Hall, M., et al., ACM SIGKDD Explor. Newsl., 2009,, 0 8. [3] Shi, L., et al., Nat. Biotechnol., 200, 28, 827 838. [4] Wang, H., et al., Chemom. Intell. Lab. Syst., 205, 46, 464 47. [5] Uhlén, M., et al., Science. 205, 347, 26049. 致谢感谢国家自然科学基金 (NO. 2575094,NO. 26754) 对该工作的支持 249

P-2-006 A variable selection method based on bat algorithm for near spectral analysis Peng Liu, Xihui Bian *, Junfu Wei, Wenqiang Wang State Key Laboratory of Separation Membranes and Membrane Processes, School of Environmental and Chemical Engineering, Tianjin Polytechnic University, Tianjin, 300387, P. R. China *Email: bianxihui@63.com Near infrared (NIR) spectroscopy combined with multivariate calibration has been widely used for the quantitative analysis of complex samples in petrochemical, agricultural, pharmaceutical and other fields []. The quality of a multivariate calibration model mainly depends on the quality of both samples and variables. However, NIR spectra are typically consisted of weak, non-specific and overlapped bands and in each NIR spectrum, thousands of variables are measured. Some of the variables may be irrelevant variables for multivariate calibration. Better calibration models may be obtained by selecting characteristic variables instead of the full-spectrum [2]. The essence of variable selection for multivariate calibration is to determine a variable subset with which the established model gives the minimum predictive errors. Although many methods such as genetic algorithm (GA), uninformative variable elimination (UVE), Monte Carlo-UVE (MC-UVE), randomization test (RT) have been proposed [3,4], the variable selection problem is a NP-hard problem. It is necessary to develop new variable selection method. Bat algorithm (BA), as a new nature-inspired meta-heuristic algorithm, was proposed by Yang [5] in 200, based on the echolocation behaviour of bats. In spite of high abilities of BA, this algorithm was entered to the field of chemistry with some delay, and only a few publications based on BA have been reported in the chemical literature. This work firstly introduced BA for NIR spectral variable selection. The iteration times, sound, frequency and bat number of the method are investigated firstly. Then BA is used to determine variable subset by the optimal parameters. Finally, the selected variables are used to build PLS model. The performance of BA is compared with UVE, MC-UVE and RT by four NIR spectral datasets. Results shows that the PLS model built using the variables selected by BA can give much better predictive accuracy than those of UVE, MC-UVE and RT. However, BA takes more time than its competitors for a same dataset. Keywords: Near infrared; Multivariate calibration; Variable selection; Bat algorithm Acknowledgements: This study is supported by National Natural Science Foundation of China (Nos. 24050, 260360 and 5678409). References: [] Sakudo, A. Clin. Chim. Acta 206, 45: 8-88. [2] Zou, X.B.; Zhao J.W.; Povey, M.J.W.; Holmes, M;. Mao, H.P. Anal. Chim. Acta, 200, 667: -2. [3] Cai, W.S.; Li, Y.K.; Shao, X.G.; Chemom. Intel. Lab. Syst. 2008, 90: 88-94. [4] Xu, H.; Liu, Z.C.; Cai, W.S.; Shao, X.G. Chemom. Intel. Lab. Syst. 2009, 97: 89-93. [5] Yang, X.S. Stud. Comput. Intell. 200, 284: 65-74. 250

P-2-007 The label-free ratiometric fluorescent aptamer sensor based on the quantitative fluorescence model and dual wavelength monitoring for the detection of Pb 2+ in environment water samples Qing Liu, Cai-Xia Shi 2,Zeng-Ping Chen* College of Chemistry and Chemical Engineering,Hunan University, Yuelu District,Changsha, 40082 2 College of Chemistry and Chemical Engineering,Hunan University, Yuelu District,Changsha, 40082 * E-mail : zpchen2002@hotmail.com Abstract: In this work, a ratiometric fluorescent aptamer sensor was developed to achieve the simple, rapid and label-free detection of Pb 2+ based on the quantitative fluorescence model (QFM) and dual wavelength monitoring. SYBR Green I (SGI) dye was used as one of signal probe due to its high specificity for dsdna and bright fluorescence upon intercalation into dsdna, while zinc protoporphyrin IX (ZnPPIX) could bind with G-quadruplex to give a strong fluorescence. In the presence of Pb 2+, G-rich DNA probe formed Pb 2+ -stabilized G4 structure, leading to the release of SYBR Green I which caused a degressive fluorescence intensity of SGI, at the same times, the fluorescence signal of ZnPPIX appeared a increased trend.the limit of detection (LOD) and limit of quantification (LOQ) were estimated to be 8.nM and 54.9nM, respectively, with recoveries of QFM model at 96.3~05.9% for concentration prediction of lead ion in enviromental water samples. This excellent results showed that the ratiometric fluorescent aptamer sensor based on the quantitative fluorescence model (QFM) and dual wavelength monitoring can be a competitive quantitative analysis method for the detection of Pb 2+ in real samples. Figure:Schematic illustration of the label-free fluorescence aptamer sensor for the detection of Pb 2+. Keywords: Ratiometric fluorescent aptamer sensor; Quantitative fluorescence model; Pb 2+ References: []Li T, Dong S, Wang E. Journal of the American Chemical Society, 200, 32(38): 356-357. [2]Kong L, Xu J, Xu Y, et al. Biosensors and Bioelectronics, 203, 42: 93-97. [3]Xu L, Shen X, Hong S, et al.chemical Communications, 205, 5(38): 865-868. 25

P-2-008 基于独立成分分析的多仪器模型转移方法刘言,*, 夏珍珍 2 武汉轻工大学食品科学与工程学院, 湖北省武汉市常青花园学府南路 68 号,430023 2 湖北省农业科学院农业质量标准与检测技术研究所, 武汉市洪山区南湖瑶苑特 号,430064 *Email: liuyanwhpu@63.com 作为一种简单 快速 无损和绿色的分析技术, 近红外光谱分析在工农业生产的各个领域得到了广泛的应用 而随着近红外光谱分析技术在各个领域中应用规模的扩大, 越来越多的情况下需要使用多台光谱仪器采集光谱 而不同仪器上收集得到的光谱之间往往存在着差异, 直接使用一台仪器上的模型对另一台仪器上的光谱进行预测往往会导致较大的分析误差 本文基于独立成分分析算法发展了一种多仪器模型转移方法 该算法将不同仪器的光谱连接成组合矩阵, 使用独立成分分析对组合矩阵进行分解, 得到混合矩阵和不同仪器的独立成分, 通过对不同仪器的独立成分系数进行修改, 实现不同仪器光谱的转移校正 使用两组数据对该算法进行检验, 结果表明, 多台仪器的光谱可以同时实现转移, 目标机光谱通过转移之后得到的转移光谱与源机光谱在主成分得分上不存在明显的差异 ; 同时, 使用转移光谱和使用源机光谱建立的偏最小二乘模型对待测组分进行预测, 可以得到较好的预测结果 该算法实现了多台近红外光谱仪器光谱的同时校正, 对于近红外光谱在工业领域的深入应用提供了理论支持 Fig. Transfer results of the spectra measured on four instruments in PC-PC2 space 关键词 : 近红外光谱 ; 独立成分分析 ; 模型转移 ; 多仪器校正 参考文献 [] Liu, Y.; Cai, W. S.; Shao, X. G. Spectrochim. Acta A 206, 69: 97. [2] Liu, Y.; Cai, W. S.; Shao, X. G. Anal. Chim. Acta 204, 836: 8. [3] Wang, J. J.; Li, Z. F.; Wang, Y.; Liu, Y.; Cai, W. S.; Shao, X. G. Spectroscopy Letters, 206, 49: 348. 252

P-2-009 Post-modified NMF 解卷积异质化临床样本以获得特定细胞类型的基因表达柳媛, 梁羽, 匡启凡, 谢凡凡, 郝颖异, 文志宁,*, 李梦龙,* 四川大学化学学院, 四川省成都市武侯区望江路 29 号,60064 *Email: liml@scu.edu.cn,w_zhining@63.com 纯细胞的信息的缺乏往往限制了计量学在临床数据上的运用, 为此有监督学习算法开始用于估算异质化样本中特定细胞类型的基因表达情况 其中非负矩阵分解算法 (non-negative matrix factorization,nmf) 是常用手段之一, 前人往往关注于估算特定细胞种类的表达值, 而相应细胞种类在异质化样本中的比例以及所得数据的校正仍然需要进一步探索 基于此现状我们改进非负矩阵分解算法, 提出了一种预修正的非负矩阵算法 (Post-modified NMF), 它能够在没有先验参考信息的情况下对临床样本的基因表达谱去卷积, 估算并校正特定细胞类型的基因表达值的同时估算出相应细胞类型在样本中的比例 首先,Post-modified NMF 运用于二组分和三组分的模拟数据集以验证和评估算法可靠性, 进一步应用于癌症样本的基因表达谱中 算法在验证和应用阶段均呈现出较为满意的结果 在验证部分, 估算值与真实值有较高的一致性, 相关系数均高于 0.99 而应用部分, 三种癌症样本在卷积后, 癌症相关的细胞类型被 提纯 出来, 这类细胞类型的表达值被用于后续的差异性基因筛选和和癌症相关基因集富集分析, 并与未去卷积的原始数据进行比较 相较于原始表达值, 提纯 后的表达值获得了更多的差异性表达基因, 且在基因富集分析中得到了之前未找到的与癌症密切相关的基因集 进一步, 算法估算的细胞类型比例在预后不同的病人组中呈现出了合理的比例差异 结果表明,Post-modified NMF 可以有效的提取和估算特定细胞类型的在异质化样本中的基因表达谱和比例, 以便更好的开展后续分析和预测 Post-modified NMF 对临床预后的深入研究以及化学计量学算法的迁移应用是有促进作用的 关键词 : 癌症 ; 非负矩阵分解 ; 去卷积 ; 基因表达 ; 预后 参考文献 []Zhao, Y.; Simon, R.; Genome Med. 200, 2: -3. [2]Shenorr, SS. ;Gaujoux, R.; Curr Opin Immunol. 203, 25: 57-578. [3]Zhang, J.; Zhang, L.; Yang, G. Chemom Intel Lab Syst. 203,26: 00-07. 致谢感谢国家自然科学基金 (NO. 2575094,NO. 26754) 对该工作的支持 253

P-2-00 Discrimination of Acori Tatarinowii Rhizoma from two habitats based on GC-MS fingerprinting and Lasso-PLS-DA Shasha Ma, B Zhang 2, L Yi,* Yunnan Food Safety Research Institute, Kunming University of Science and Technology, Kunming, 650500, P.R. China 2 School of Science, Kunming University of Science and Technology, Kunming, 650500, P.R. China * E-mail: yilunzhao@kmust.edu.cn. This study aims to explore the chemical differences of Acori Tatarinowii Rhizoma (ATR) samples collected from two habitats, Sichuan and Anhui provinces, China. Gas chromatography-mass spectrometry (GC-MS) was applied to establish the quantitative chemical fingerprints of ATRs. A total of 04 volatile compounds were identified and quantified with the information of mass spectra and retention index (RI). Furthermore, least absolute shrinkage and selection operator (Lasso), a sparse regularization method, combined with subsampling was employed to improve the classification ability of partial least squares-discriminant analysis (PLS-DA). After variable selection by Lasso, three chemical markers, β-elemene, α-selenene and α-asarone, were identified for the discrimination of ATRs from two habitats, and the total classification correct rate was increased from 82.76% to 96.55%. The proposed Lasso-PLS-DA method can serve as an efficient strategy for screening marked chemical components and geo-herbalism research of traditional Chinese medicines. Fig. Variable selection of the 04 volatile components. (A), (B) and (C) are VIP values, coefficients β and selection frequency of Lasso for the 04 components. (D) are Correct rates of the PLS-DA models established by different combinations of variables. The correct rate was obtained from the 0-fold cross validation. The best correct rate was obtained by the combination of the first three variables. Key words: Acori Tatarinowii Rhizoma; Gas chromatography-mass spectrometry; Least absolute shrinkage and selection operator; Partial least squares- discriminant analysis References: [] Zhang, X.; Yi, L.; Deng, B.; Chen L.; Shi S.; Zhuang, Y.; Zhang, Y. J. Sep. Sci. 205, 38: 4078-4085. [2] Yi, L.; Dong, N.; Yun, Y.; Deng, B.; Ren, D.; Liu, S.; Liang, Y. Ana. Chim. Acta. 206, 94: 7-34. [3] Fu, G.; Zhang, B.; Kou, H.; Yi, L. Chemometr. Intell. Lab. 207, 60: 22-3 254

P-2-0 太赫兹光谱结合化学计量学鉴别木材种类研究邵常艳, 张欣 2 *, 张卓勇 首都师范大学, 北京,00048,E-mail:260702075@cnu.edu.cn 通讯作者邮箱 :gusto2008@vip.sina.com 木材市场上的木材种类繁多, 不同的质地决定了其特有的加工性能, 加之不同品种稀有程度差异巨大, 也导致不同材质价格悬殊 木材品种的判别仅通过人的主观判断难以实现, 市场上对木材的鉴别主要是建立在对木材进行磨粉 切块的基础上, 覆盖面少且耗时耗力 [] 太赫兹是一种能透过大多数非金属和非极性物质传播的电磁波 [2], 与微波 X 射线 核磁共振成像相比, 太赫兹所在区域振动能量低, 不会对样品造成电离损伤, 适合于生物样品以及其他贵重材料的检测 同时太赫兹波谱能够提供以往检测方法中难以响应的分子的弱相互作用, 例如氢键 范德华力等, 能够获取测定样品中特有的化学信息 [3] 因此本文拟应用太赫兹光谱技术结合化学计量学的方法实现对木材快速无损的检测 本文通过计算太赫兹时域光谱的可选择参数, 包括时域光谱最大响应值 最小值 次最大响应值 最值斜率等, 结合变量选择和多变量分析, 对不同品种的木材进行了分类研究 结果表明, 通过主成分分析 (PCA) 和层次聚类分析 (HCA) 两种无监督分类方法可以获得部分品种的正确分类, 与植物学分类相吻合 通过偏最小二乘判别 (PLS-DA) 和支持向量机 (SVM) 两种有监督分类方法能够获得较好的木材分类结果, 在一定程度上能够满足市场对木材分类和造假判别的需求 关键词 : 太赫兹时域光谱技术 ; 化学计量学 ; 木材 ; 品种 参考文献 [] 张雯雅. 近红外光谱技术在珍稀木材鉴别领域的研究与应用.205: [2]Johh F Federci.;Brian Schulkin.; Feng Huang.;Dale Gary.Semicond. Sci. Technol 2005,20:S266 [3] 张蕾 ; 徐新龙 ; 李福利. 量子电子学报,2005,22(2):29 255

P-2-02 Combining the Suitability Score and Successive Projection Algorithm for Variable Selection in Partial Least-squares Discriminant Analysis Zhiying Wang, Weimin Shi, Qi Shen,* College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, 450052, China *Email: shenqi@zzu.edu.cn Abstract Infrared spectroscopy (IR) technique combined with multivariate statistical analysis methods is widely used in fundamental and applied chemical research. The selection of variables is a key step in developing a successful multivariate analysis system. In this study, the suitability score combined with successive projections algorithm (SPA-S) was proposed for variable selection. SPA is firstly used to removal high collineraity variables and then the suitability scores is used for selection informative variables. Using these selected variables, partial least-squares discriminant analysis (PLSDA) model is constructed to evaluate the performance of SPA-S. The proposed approach is applied to analyze the near infrared spectroscopy of six tea varieties and Fourier transform infrared spectroscopy of different kinds of edible vegetable oils. The results of SPA-S (SPA-S-PLSDA) were compared to those obtained by the suitability scores (S-PLSDA), successive projections algorithm (SPA-PLSDA) and PLSDA with all variables. The comparison demonstrated that SPA-S-PLSDA can perform good prediction performance and is an efficient tool for mining high dimension data. Keywords: Partial least square discriminant analysis, variable selection, successive projections algorithm, the suitability score References: [] Shen Q., Shi W., Kong W. J. Biomed. Inform. 2009, 42:59. 256

P-2-03 Novel calibration models for quantification of DNA in biological samples by mass spectrometry based Exonuclease III-assisted recycling amplification Cai-Xia Shi, Chen 2 *, Liu and Yu College of Chemistry and Chemical Engineering, University of Hunan, Yuelu District, Changsha, 40082 2 College of Chemistry and Chemical Engineering, University of Hunan, Yuelu District, Changsha, 40082 zpchen@hnu.edu.cn; zpchen2002@hotmail.com (Z.P. Chen) Abstract: In this contribution, an accurate mass spectroscopy quantitative determination platform was developed for target DNA in complex biological samples (i.e., urine and serum) based on a novel multiplicative effects model for free of internal standard integrated with single-step Exo III-assisted target recycling amplification strategy. The design of this method was to reduce the undesired false-positive results in spectroscopy detection for the signals of the spectroscopy easily sufferd from matrix interferences possibly in practical detection. And the activity analysis of Exonuclease III for single-stranded DNA was definitely demonstrated and a excellent specific rule was drawn for double-stranded DNA with mismatched bases firstly in this paper. More importantly, the proof-of-concept platform achieved a rather accurate quantitative analysis of target DNA in practical complex biological system based on the multiplicative effects model for free of internal standard developed on mass spectra data in ideal buffer solution with the recovery rates range of 92.6 ~ 3. % and ARPE value of not more than 8. % that far superior to the corresponding results of 3.8 ~ 68.8 % of PLS model. The superior performance of accuracy, practicability and robustness of the developed platform render the model to broader potential application for more practical significant nucleic acid research. Fig. Schematic illustration of Exo III-assisted signal amplification strategy integrated MS technology for target DNA detection Keywords: Multiplicative effects model for free of internal standard; Mass spectrometry; Signal amplification; DNA biosensor; Quantitative analysis References: [] Du, H.; Chen, Z.; Song, M.; Chen,Y.; Yu, R. Journal of Chromatography A, 204, 338(8), 44-50 [2] Shi, C.; Chen, Z.; Chen, Y.; Yu, R. Analytical Methods, 205, 7(6): 6804-6809 [3] Hu, Y., Chen, Z., Chen, Y., Shi, C., Yu, Q. Journal of Chromatography A, 206, 445, 2-7 [4] Li, Y., Zhao, Q., Wang, Y., Man, T., Zhou, L., Fang, X., Liu, J. Analytical chemistry, 206, 88(23), 684-690 257

P-2-04 Adaptive Window Size Savitzky-Golay Smoothing Xiting Sun, Hongfu Yuan * College of Material Science and Engineering, Beijing University of Chemical Technology, Beijing 00029, China *Email: yhf204@26.com Data smoothing is of great importance for chemical signal pretreatment. Although the Savitzky-Golay(SG) algorithm has become an almost universal method to smooth any kind of signal, there may be room to improve it because of improper parameters selected artificially, such as window size. In order to automatically select the optimal window size of the SG algorithm, a new approach named adaptive window size Savitzky-Golay algorithm is proposed in the present work. The method is based on the comparison of the polynomial fitting residuals with the noise of the instrument. The optimal window size is defined as one that yields the residual closest to the noise of the instrument. The method is applied in two steps. In the first step, the noise of the instrument is computed through the study of a blank signal. In the second step, the SG algorithm is applied to smooth the signal using different window size point by point. The performance of the proposed procedure was evaluated by a simulated dataset together with a near-infrared spectral dataset and was shown to be robust. The results reveal optimal window size depends on local spectral feature (e.g. peak-shape of the signal and noise variance) and adaptive window size SG algorithm performs better than fixed window size one. Keywords: Savitzky-Golay algorithm; adaptive window size; signal analysis; smoothing techniques References [] Savitzky, A; Golay, M. J. E. Anal. Chem.964,36: 627. [2] Gabriel, V; Peter, J. S. Anal. Chem.2006,78: 4598. [3] Schneider, R. C.; K zovar, K. A. Forensic Sci. Int. 2003, 34: 87. [4] Jonsson, P.; Eklundh, L. Comput. Geosci. 2004, 30: 833. [5] Massart, D. L.; Vandeginste, B. G. M.; Buydens, L. M. C.; de Jong, S.; Lewi,P. J.; Smeyers-Verbeke, J. Handbook of Chemomentrics and Qualimetrics, Part A; Elsevier: Amsterdam, 998; Chapter 20. 258

P-2-05 VEGFR2 与药物分子的结合模式及作用机制的分子动力学模拟研究王宇, 王进安 2, 罗勇锋, * 2 朱维良, * 中南林业科技大学, 湖南省长沙市韶山南路 498 号,40000 2 上海药物研究所, 上海市浦东新区张江镇祖冲之路 555 号,200000 * lyfnku@63.com(yl); E-mail:wlzhu@simm.ac.cn(WZ) 血管内皮生长因子受体 2(VEGFR2) 是酪氨酸激酶受体家族中的一员,VEGFR2 的异常调节和变异在许多人类疾病中发挥重要作用, 是治疗癌症的重要靶标 [] VEGFR2 的保守区域 ASP-PHE-GLY(DFG) 有 DFG-in 活化构象和 DFG-out 非活化构象 根据抑制剂与 VEGFR2 的不同结合模式, 可以将其抑制剂划分为 Ⅰ 类,Ⅱ 类等不同种类抑制剂 在 DFG-in 构象中靶向 ATP 结合口袋的抑制剂是 Ⅰ 类抑制剂, 如药物分子 Lenvitinib(LEV); 而药物分子 Sorafenib(BAX) 和 Sunitinib(B49) 则在其 DFG-out 构象中, 靶向 ATP 结合口袋, 是 II 类抑制剂 [2] 因此, 探究这些药物分子与 VEGFR2 蛋白的结合机制将有助于设计结构新颖和高选择性的抑制剂 本文综合使用长时间分子动力学模拟, 主成分分析及结合自由能计算等方法, 详细研究了这些药物分子与靶蛋白 VEGFR2 的结合模式及结合能力 研究表明, 不同类型的药物分子与 VEGFR2 的结合有显著差异, 如 Ⅰ 抑制剂 LEV, 其与 VEGFR2 的活化及非活化构象都可有效结合, 而 II 类抑制剂 BAX 和 B49 则更倾向于与 DFG-out 构象结合 此模拟结果也提示在药物分子设计过程中需要综合考虑抑制剂分子与靶标蛋白不同功能构象的结合情况, 以获取性能更为优良的抑制剂 关键词 : 血管内皮生长因子受体 ; 抑制剂作用机制 ; 分子动力学模拟 ; 药物设计参考文献 : [] Folkman, J. Nat. Med. 995,, 27-3. [2] Robert Roskoski Jr, Pharmacol. Res. 206, 03, 26-48. 259

P-2-06 DeepMirTar: a deep-learning approach for predicting human mirna targets Ming Wen, Peisheng Cong 2, Zhimin Zhang, Hongmei Lu, *, and Tonghua Li 2, * College of Chemistry and Chemical Engineering, Central South University, Changsha 40083, PR China 2 School of Chemical Science and Engineering, Tongji University, Shanghai 200092, PR China * Email: hongmeilu@csu.edu.cn, lith@tongji.edu.cn ABSTRACT MicroRNAs (mirnas) are small noncoding RNAs that function in RNA silencing and post-transcriptional regulation of gene expression by targeting messenger RNAs (mrnas). Because the underlying mechanisms associated with mirna binding to mrna are not fully understand, a major challenge of mirna studies involves the identification of mirna-target sites on mrna. In silico prediction of mirna-target sites can expedite costly and time-consuming experimental work by providing the most promising mirna-target-site candidates. Currently, there exists a model combining expert design features and shallow machine-learning methods, like random forest, support vector machine, and Gaussian process. Although these methods improved the performance of mirna-target prediction, there remains significant room for improvement. In this study, we reported the design and implementation of DeepMirTar, a deep-learning-based approach for accurately predicting human mirna targets at the site level. The predicted mirna-target sites are those having canonical or non-canonical seed, and features, including high-level expert-designed, low-level expert-designed, and raw data level, were used to represent the mirna-target site. Comparison with other state-of-the-art machine-learning methods and existing mirna-target-prediction tools indicated that DeepMirTar improved overall predictive performance. Keywords: mirna targets prediction, deep learning, semi-supervised learning 260

P-2-07 拉曼高光谱成像结合化学计量学分析绿豆萌发过程代谢研究吴祺琤, 张欣, 张卓勇 * 首都师范大学, 北京市海淀区西三环北路 05 号,00048 *Email: gusto2008@vip.sina.com 种子萌发不仅与粮食产量息息相关 [], 还对植物种质资源保存与植物种族的延续有重大意义, 影响种子萌发的因素以及种子萌发过程中的生理生化变化都是种子萌发的研究重点 拉曼光谱是基于光子激发振动发生非弹性散射而建立起来的一种快速无损的光谱技术, 其具有指纹识别特征, 能从分子水平获得物质的结构及组成信息, 适用于对生物体系的研究 通过高光谱成像的方式还能从空间分布的角度更为全面地分析种子萌发过程中的细胞分化过程 本文基于拉曼高光谱成像研究了绿豆种子萌发过程中光照 营养素 ( 氮元素 ) 等因素对其代谢组学变化规律的研究 绿豆萌发主要分为 :() 吸胀准备期 (0~3h, 吸胀缓慢 ) (2) 萌发前期 (3~9h, 吸胀速率加快 ) (3) 萌发中期 (9~4h, 吸胀速率缓慢 ) (4) 萌发准备期 (4~6h, 吸胀速率加快 ) (5) 后萌发期 (6h~, 胚根生长期, 吸胀速率加快 ) [-2] 本实验在绿豆萌发的不同阶段对萌发绿豆的子叶和胚根切片进行拉曼成像测试, 并与未萌发的绿豆进行比较 对取得的拉曼光谱数据运用主成分分析法 (Principal Component Analysis, PCA), 偏最小二乘判别分析法 (Partial Least Squares Discriminant Analysis, PLS-DA) 以及正交偏最小二乘判别分析法 (Orthogonal Partial Least Squares Discriminant Analysis, OPLS-DA) 进行多变量 ( 光照及营养素 ) 对绿豆不同萌发阶段的拉曼光谱进行统计分析 此外, 通过多元曲线分辨交替最小二乘 (Multivariate Curve Resolution Alternating Least Squares, MCR-ALS) 提取了不同发育状态下的相应主成分特征光谱及其对应根部细胞变化特征, 为研究种子萌发过程代谢组学提供了新的研究方法 关键词 : 萌发 ; 拉曼高光谱 ; 化学计量学 ; 代谢组学 参考文献 : [] Bewley, J. D. The Plant Cell 997, 9: 055. [2] Nonogaki, H.; Bassel, G. W.; Bewley, J. D. Plant Science 200, 79: 574. * 北京市科技创新平台项目 (75303900) 资助 26

P-2-08 Investigation on the binding mechanism of loratinib with the c-ros oncogene (ROS) receptor tyrosine kinase via molecular dynamics simulation and binding free energy calculations XiaoYun Wu*, YuanYuan Wang, ShanHe Wan, JiaJie Zhang* Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 5055, PR China * E-mail: xywu@smu.edu.com(xy Wu); zhangjj@smu.edu.cn (JJ Zhang) The c-ros oncogene (ROS) has proven to be an important cancer target for the treatment of various human cancers. The anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been granted approval for the treatment of patients with ROS positive metastatic non-small-cell lung cancer (NSCLC) by the Food and Drug Administration (FDA) on 206. However, serious resistance due to the secondary mutation of G2032 to arginine (G2032R) was developed in clinical studies. Loratinib (PF-06463922), a macrocyclic analogue of crizotinib, showed significantly improved inhibitory activity against ROS and ROS G2032R.To provide insights into the inhibition mechanism, molecular dynamics simulations and free energy calculations were carried out for the complexes of loratinib with wide-type (WT) and G2032R mutated ROS. MD simulations indicated that the G2032R system is more flexible compared with WT system. Calculations of binding free energies indicate that G2032R mutation significantly reduces the binding affinity of loratinib for ROS, which arose mostly from the increase of conformation entropy and the decrease of solvation energy. Furthermore, detailed per-residue binding free energies highlighted the increased and decreased contributions of some residues in the G2032R systems. The present study revealed the detailed inhibitory mechanism of loratinib as potent ROS inhibitor, which was expected to provide a basis for rational drug design. Keywords: Molecular dynamics (MD), binding free energy calculation, ROS inhibitor, loratinib Acknowledgements We acknowledge the financial supports from the National Natural Science Foundation of China (No.820243 and No. 8573263) and National Natural Science Foundation of Guangdong, China (No. 205A03033285). References: [] Johnson T.W., Richardson P.F., Bailey S.,et al. J Med Chem, 204, 57: 4720-4744 [2] Zou H.Y., Li Q., Engstrom L.D, et al. Proc Natl Acad Sci USA, 205, 2: 3493-3498 [3] Pathak D., Chadha N., Silakari O. J Mol Graph Model, 206, 70: 85-93 262

P-2-09 激光诱导击穿光谱技术结合核极限学习机以及变量选择方法用于煤灰分 挥发分以及热值的快速测定闫春华, 张天龙, 汤宏胜, 李华,2,* 西北大学化学与材料科学学院分析科学研究所, 陕西, 西安,70069 2 西安石油大学化学化工学院, 陕西, 西安,70065 *Email: huali@nwu.edu.cn 煤作为世界上主要的化石能源, 可被用作能源资源, 燃烧用来发电发热, 也可以用于工业方面, 例如冶金工业 煤灰分 挥发分以及热值是评价煤质的重要指标, 对煤的价格 化学燃烧性能以及其适用性有着重要影响 因此, 对煤灰分 挥发分以及热值进行快速分析, 对于快速评价煤的质量 价格及其用途, 实现煤炭的高效清洁应用具有重要意义 激光诱导击穿光谱 (laser-induced breakdown spectroscopy, LIBS) 作为一种光学发射光谱技术, 具有快速 多元素同时分析 无需复杂样品准备过程 无损分析以及原位分析等特点 核极限学习机 (kernel extreme learning machine, K-ELM) 是一种相对较新的非线性分析方法, 具有学习速度快 泛化性能好等优点, 已在分类和回归问题中表现了其优异的性能 本文利用 LIBS 结合 K-ELM 对煤灰分 挥发分以及热值进行快速分析, 采用连续投影算法 (successive projections algorithm, SPA) 以及粒子群 (particle swarm optimization, PSO) 算法进行特征波长选择, 以所选取的特征波长作为输入变量, 建立 K-ELM 定量模型对煤灰分 挥发分以及热值进行快速测定 结果表明, 基于特征波长的 K-ELM 模型结果优于基于全谱的 K-ELM 模型, 其中 PSO-K-ELM 模型的预测效果最佳, 预测集相关系数都在 0.99 以上 故 LIBS 结合 PSO-K-ELM 是一种煤质快速分析的高效分析方法且有助于实现煤炭工业的在线快速分析 Fig. An overview of the analysis process. 关键词 : 激光诱导击穿光谱 ; 核极限学习机 ; 煤 参考文献 [] Huang G. B.; Zhu Q. Y.; Siew C. K. Neurocomputing, 2006, 70: 489-50. [2] Hou Z. Y.; Wang Z.; Yuan T. B.; Liu J. M.; Li Z.; Nie W. D. J. Anal. At. Spectrom., 206, 3(3): 722-736. 本工作得到了科技部重大仪器设备开发专项 (No. 20YQ0303) 和国家自然科学基金 (No. 237505, 260523) 的支持 263

P-2-020 C8H8 同分异构与沸点的 QSPR 研究杨林卫旭琴雷菲王琼瑶杨林 * 青海师范大学青海西宁 80008 * yanglin@qhnu.edu.cn 摘要 :C8H8 化合物的同分异构体共有 8 种, 结构不同性质存在差异 根据 C8H8 同分异构体的空间坐标, 应用 Chem window 6.0 和 Chem Office 2008 化学软件, 绘制出一系列 C8H8 分子的 3D 结构图, 确定各原子的空间点位 A(x,y,z), 根据能量最低原理计算得到稳定分子空间构型, 选择具有代表性的官能团原子作为坐标原点 O(x,y,z), 得到所有原子坐标点位集合成的分子矩阵 M, 计算各原子到原点的空间距离的均值得到 Ys, 计算 M 的 Frobenius 范数得到 Yf 结果表明 Ys 与 Yf 的值与熔点 沸点和相对密度有关, 因此对 C8H8 的物化性质预测有良好的效果 自定义原子距离指数和分子空间特征指数, 结合分子中的甲基数 乙基数以及 Wiener 指数和 Randic 分子连接性指数与 C8H8 的十八个同分异构体的沸点建立多元线性回归模型, 并分析结构与性质的相关性, 为同分异构体的 QSPR 研究提供新的思路 关键词 :C8H8; 同分异构 ; 沸点 ;QSPR 参考文献 [] 王化云, 江元生. 应用拓扑指数预测化学性质 [J]. 化学通报,992,():6- [2] 李冀, 吴超. 基于 QSPR 法的脂肪醇化合物闪电预测 [J]. 中国安全科学学报,202 [3] 张晶, 赫敏, 杨林. 拓扑指数法在 QSPR 研究中的应用.[J] 江汉大学学报,20(6) [4] 周长会, 吴启勋, 侯庆高. 一种研究脂肪胺 QSPR 的拓扑方法 [J]. 广西师范大学学报,203(2) [5] 张巍巍. 拓扑指数在化学化工领域的研究现状 [J]. 化学工程师,205(3) [6] 张尹炎, 潘鲁. 基于 QSPR 方法的烃类物质苯胺点预测 [J]. 安全与环境学报,205(2) [7] 林志芬, 混合有机物定量结构 - 活性相关 [M], 北京 : 科学出版社,2005:6-7 [8] 王晓栋, 部分有机污染物的结构 - 活性关系, 南京 : 南京大学,2002 [9] 杨娜, 杨林. 多氯联苯分子空间坐标与物性的构效关系研究 [A].20 [0] Wiener H J,J Chem Soc. 947,69:7-20 [] Randic M.J Chem Inf Comput Sci,986,26:34-36 264

P-2-02 基于结构模体和在线学习策略的蛋白质二级结构预测 * 印春凯, 周鹏杰, 丛培盛, 李通化同济大学, 上海市杨浦区四平路 239 号, 邮编 :200000 lith@tongji.edu.cn 人类在蛋白质二级结构预测的领域已经做了许多的工作, 取得了丰富的研究成果, 一些优秀的预测方法准确率已经超过了 80%, 表明不以繁琐昂贵的实验手段来获取蛋白质的结构是可行的 我们发现现有的大多机器学习预测方法, 对于同源性较高的蛋白质表现十分出色, 而对于同源性较低的目标蛋白则显得力不从心, 具体表现为对实验方式测得的新蛋白预测准确度的下降 本文提出一种基于结构模体 (Structure-Motif) 结合在线学习策略的方法, 针对蛋白质同源性高低采用不同的变量进行预测 采集 205 年之前 PDB 中发布的蛋白质数据建立模板库和模体库, 采用两种不同的方式建模 预测时, 用 PSI-BLAST [] 进行序列比对, 分别处理, 方法流程如图 : 图 程序流程图 Score>60 为高同源序列 : 使用 PSI-BLAST 比对模板库, 得到 SPSSM [2, 3] 作为变量, 运用条件随机场进行预测 SPSSM 是我们曾经提出的一种基于 PSSM 的新变量, 能够最大程度地反映序列之间的同源性信息 Score<60 为低同源序列 建模时定义具有 长度为 9, 且中心处结构唯一 性质的氨基酸片段为结构模体, 并建立相应模体数据库 (9mer Database), 经统计其结构唯一性高达 99.8% 预测时待预测序列切片通过与结构模体库的 CDHIT 聚类信息 最邻近模体的 BLUSOM62 代换得分向量作为预测变量, 用条件随机场进行预测 由于模体来源于不同蛋白质, 因而避免了同源建模方法中, 比对整条蛋白所面临的同源性过低的尴尬 本方法定期自动采集 PDB 最新数据, 实现模型在线学习, 模板库 模体库自更新, 经验证, 在 9 个月对于 PDB 新增数据的学习之后, 本方法对于原测试集的预测准确从 72% 上升为 94% 本项目由国家自然科学基金项目资助编号 :227508 关键词 : 结构模体 蛋白质二级结构 SPSSM CDHIT 参考文献 : [] Stephen F. Altschul*. et al., Gapped BLAST and PSLBLAST: a new generation of protein database search programs. Nucleic Acids Research, 997.25(7): p.3389-3402 [2] Cong, P., et al., SPSSM8: an accurate approach for predicting eight-state secondary structures of proteins. Biochimie, 203. 95(2): p. 2460-4. [3] Li, D., et al., A novel structural position-specific scoring matrix for the prediction of protein secondary structures. Bioinformatics, 202. 28(): p. 32-9. 265

P-2-022 手机摄像系统结合化学计量学检测食品饮料中偶氮类色素含量于洋, 张欣, 张卓勇 * 首都师范大学, 北京市海淀区西三环北路 05 号,00048 *Email: gusto2008@vip.sina.com 食品在加工的过程中容易丢失原本的颜色, 食品加工者为了使食物看起来更美味, 会向其中添加廉价的合成色素 偶氮类色素是指色素分子结构中至少含有一个偶氮基 (-N=N-) 结构的色素, 但对人体存在致癌风险 目前常用的检测方法有传统的液相色谱法和分光光度法等, 色谱法耗时长, 检测步骤复杂, 而分光光度法, 所需仪器简单, 但检测限较低 开发出对偶氮类色素快速 准确的检测方法是非常必要的 -2 本文研究了通过手机摄像系统得到的数码图像来检测饮料中偶氮类色素浓度的方法 使用不同浓度单一色素和混合色素, 以及它们在不同 ph 条件下的图像发生颜色变化的数码图像, 构建 RGB 三通道的像素数据矩阵, 应用偏最小二乘 (PLS) 和多维偏最小二乘 (N-PLS) 3 方法建立可同时预测以碳酸饮料为代表的混合体系中多种色素浓度的校正模型 其中, 高维的多维偏最小二乘方法 (N-PLS) 由于同时考虑自变量矩阵和应变量矩阵的信息, 可以有效解决高维数据的建模问题, 具有较好的模型预测和推广能力 苋菜红预测浓度和实际浓度之间的 R 2 为 0.940, 柠檬黄预测浓度和实际浓度之间的 R 2 为 0.92, 胭脂红预测浓度和实际浓度之间的 R 2 为 0.905 相比现在常用的检测偶氮类色素的方法, 本文提出的方法检测快速 准确, 能够通过诸如手机摄像系统的便携式设备实现检测, 无需大型试验仪器易于操作 关键词 : 手机摄像系统 ; 偶氮类色素 ; 偏最小二乘 ; 多维偏最小二乘 参考文献 [] Yamjala, K.; Nainar, M S.; Ramisetti, N R. Food Chemistry. 206, 92: 83. [2] 薛虎寅, 尹永梅, 张太昌等. 生物技术进展, 202, 2(3): 7. [3] Andersson C A; Bro R. Chemometrics and Intelligent Laboratory Systems. 2000, 52():. * 北京市科技创新平台项目 (75303900) 资助 266

P-2-023 The influence of class-imbalance ratio, data dimension and variable correlation for classification of metabolomics data Bing-Yang Zhang a, G Fu a*, L Yi b* a School of Science, Kunming University of Science and Technology, Kunming, 650500, P. R. China b Yun nan Food Safety Research Institute, Kunming University of Science and Technology, Kunming, 650500, P.R. China E-mail: guanghuifu@kmust.edu.cn (G. H. Fu), yilunzhao@kmust.edu.cn (L. Z. Yi) Classification of imbalanced data is an important issue in metabolomics. How to improve the classification accuracy of imbalanced data is currently the focus of attention. This study evaluated the influence of data structure for classification of metabolomics data from three aspects: imbalanced ratio, that is to say the ratio of the negative class to the positive class, data dimension and variable correlation. The results show that these three aspects all have a great impact on the classification of metabolomics data. Along with the increase of imbalance ratio, the classification of metabolomics data is getting worse, especially the minority class. When the dimension of data becomes higher, that is, the disturbance variable is increasing; the data classification results are getting worse, in particular, under the condition of imbalanced data, the classification of the minority class become very badly. Similarly, as the correlation of variables increase, the classification of data is increasing unsatisfactory, when the imbalance ratio reaches a high level, the classification of the minority is even reduced to zero. The work done in the paper is intended to give some reference to later research on the classification of imbalanced data. Fig. The classification results obtained by SVM Chart notes: The abscissa represents the class-imbalance ratio, which is equal to the number of the minority class to the number of the majority class. The ordinate represents the average value of the 00 iterations of the accuracy. n: the number of variable; r: the correlation coefficient of variable. The first graph shows that the increase in imbalance has impact on the classification on the minority class, which has no effect on the majority class. The second graph shows that the increase in the data dimension has a significant effect on the classification of imbalance data. The last picture shows that when the variable correlation coefficient increases, the classification of the imbalance data becomes worse. Keywords: class-imbalance, imbalance ratio, data dimension, variable correlation References: [] Chawla N V, Bowyer K W, Hall L O, et al. Journal of Artificial Intelligence Research, 2002, 6():32-357. [2] Yen S J, Lee Y S. Expert Systems with Applications, 2009, 36(3):578-5727. [3] Leo Breiman. Machine Learning, 999, 45():5--32. 267

P-2-024 一种基于启发式最优伙伴波段组合的近红外光谱变量选择方法张进, 崔晓宇, 蔡文生, 邵学广 * 南开大学化学学院, 分析科学研究中心, 天津市卫津路 94 号,30007 *Email: xshao@nankai.edu.cn 变量选择的目的在于从数量繁多的待选变量中选择出具有代表性的 建模效果好的变量 其应用范围已经广泛覆盖近红外 / 拉曼光谱分析 生物标记物识别和其他社会科学分析方面 最优伙伴变量组合 [] 是指一种基于变量两两组合的变量选择方法, 该方法在一定程度上能够寻找出一组具有协同效应的最优变量组合 另一种值得注意的方法是无信息变量删除 [2], 该方法利用变量之间的正交投影大小选择出一组具有最小冗余的代表性变量 然而, 由于近红外光谱的吸收通常为具有一定宽度的峰形, 因此波段选择在解释性和利用多变量数据上具有一定的优势 我们提出了一种通过结和连续正交投影和最优伙伴变量组合的近红外光谱变量波段选择方法 该方法首先通过连续正交投影的正交特性在光谱区间上选择具有代表性的结点, 并以这些节点为中心, 以一定长度为宽度, 将近红外光谱区间划分为若干彼此相对独立并且具有代表性的波段 然后通过波段的两两 排列组合, 选择出建模过程中具有 协同效应 的波段 通过该方法对玉米 药片和土壤的近红外光谱变量选择, 并对比了连续随机投影 最优伙伴变量组合 随机测试 竞争自适应重加权采样 蒙特卡洛 无信息变量删除等变量选择方法, 结果表明该方法能够有效选择具有协同效应且包含丰富目标信息的波段, 且能够有效提升光谱建模效果 关键词 : 近红外光谱 ; 变量选择 ; 波段选择 ; 连续正交投影 ; 最优伙伴变量组合 参考文献 [] Pan T.; Han Y.; Chen J.M.; Yao L.J.; Xie J. Chemom. Intell. Lab. Syst. 206, 56: 27. [2] Araujo M.C.U.; Saldanha T.C.B.; Galvao R.K.H.; Yoneyama T.; Chame H.C.; Visani V. Chemom. Intell. Lab. Syst. 200, 57: 65. 国家自然科学基金项目 (No. 2475068) 资助 268

P-2-025 孔雀石绿及其代谢产物与血清蛋白的作用过程研究 张秋兰, 倪永年,* 南昌大学化学学院 江西省南昌市红谷滩新区学府大道 *Email: ynni@ncu.edu.cn 999 号 33003 摘要 孔雀石绿及其代谢产物(无色孔雀石绿)能迅速在组织中蓄积[], 无色孔雀石绿具有高残留和致癌 致 畸 致突变等副作用, 很多国家已经禁用, 但仍有不法分子使用无色孔雀石绿延长鱼类的存活时间[2] 本文 采用经典方程计算作用体系的常数和参数; 用红外和圆二色谱证实BSA构象的改变; 并用MCR-ALS对生命 体系测量的多维波谱数据进行解析和描述 从结果可知: 孔雀石绿及无色孔雀石绿与BSA结合常数达到06 L mol-, 血清结合率高, 在体内消除慢, 作用维持时间长, 不易代谢; 通过对荧光和圆二色谱两种光谱方法 的数据矩阵进行扩展并用MCR-ALS处理数据, 较全面地分析了无色孔雀石绿与BSA相互作用过程(Fig.), 从而得知无色孔雀石绿在内脏和组织中形成严重的蓄积性残留, 危害食品安全和人类健康 Fig. Spectra obtained from different experiments and the recovered spectra and concentration results of the simultaneous analysis of the fluorescence and CD data matrices 关键词 孔雀石绿 无色孔雀石绿 BSA 化学计量学 参考文献 [] Wang, F.; Wang, H.; Shen, Y.D.; Li, Y.J.; Dong, J.X.; Xu, Z.L.; Yang, J.Y.; Sun, Y.M.; Xiao, Z.L. J. Agric. Food Chem. 206, 64(42): 8054. [2] Jahanban-Esfahlan, A.; Panahi-Azar, V. Food Chem. 206, 202: 426. 269

P-2-026 模型集群分析 (MPA) 结合最小绝对收缩和选择算子 (LASSO) 在光谱多元校正中的应用张若秋, 杜一平 * 华东理工大学上海市功能性材料化学重点实验室, 化学与分子工程学院, 上海市梅陇路 30 号,200237 由于近红外光谱数据的变量数远大于样本数且变量之间共线性强, 利用多元线性回归方法对近红外光谱数据建模往往不能得到较好的模型 最小绝对收缩和选择算子 (LASSO) 是一种利用罚函数来提高模型预测能力的算法, 该算法使用 - 范数约束不仅能够解决高维度和共线性问题, 还能使建立的模型具有 稀疏性, 即算法在建模中具有自动进行波长选择的效果 然而在此前的部分研究工作中, 利用 LASSO 进行建模是通过对 - 范数约束条件进行优化, 但针对不同样本集合对波长选择的影响缺乏足够的研究 本工作首先在模型集群分析 (MPA) 的框架下, 利用 LASSO 对不同样本子集进行建模, 使用不同子集所选择波长的统计性质构建若干波长子集, 再利用采样误差分布分析 (SEPA) 对不同波长子集进行分析来确定最优子集, 避免了样本不同对 LASSO 建模的影响 与之前的研究相比, 本工作提出的算法提高了模型的预测能力和解释能力, 同时本工作还将利用该算法与建模算法如岭回归 (RR) 主成分回归 (PCR) 偏最小二乘回归 (PLSR) 及其他波长选择算法进行比较 关键词 : 最小绝对收缩和选择算子 ; 采样误差分布分析 ; 模型集群分析 参考文献 [] Tibshirani, R. J. R. Stat. Soc. B. 996, 58: 267. [2] Li, H.; Liang Y.; Xu Q.; Cao D. J. Chemometr. 200, 24: 48 [3] Chen, W.; Du, Y.; Zhang, F.; et al. J. Chemometr. 207, e2933. https://doi.org/0.002/cem.2933 270

P-2-027 大气污染物中多环芳烃致癌性的定性构效关系研究张天龙, 祁娟, 汤宏胜, 李华 *,2 西北大学分析科学研究所, 陕西, 西安,70069 2 西安石油大学化学化工学院, 陕西, 西安,70065 *Email: huali@nwu.edu.cn 多环芳烃 (PAHs) 是煤, 石油, 木材, 烟草, 有机高分子化合物等有机物不完全燃烧时产生的挥发性碳氢化合物, 存在于大气颗粒物中, 而迄今已发现有 200 多种 PAHs, 其中有相当部分具有致癌性, 因此研究多环芳烃的致癌性对人类健康有重要意义 定性构效关系 (QSAR) 是一种借助分子的理化性质参数或结构参数, 以数学和统计学手段定量研究有机小分子与生物大分子相互作用 有机小分子在生物体内吸收 分布 代谢 排泄等生理相关性质的方法 随机森林 (Random forest, RF) 是一种自然的非线性建模工具, 预测准确率高, 不容易出现过拟合, 是目前数据挖掘 生物信息学的热门的前沿研究领域之一 本文利用随机森林结合定量构效关系方法对大气颗粒物中多环芳烃的致癌性进行预测, 利用 45 种多环芳烃的 8 个结构参数及致癌性建立模型, 再利用所建模型对 22 种多环芳烃进行预测, 得到测试结果准确率为 90.9%, 由此推测利用随机森林结合定量构效关系分析方法可以快速有效的预测大气颗粒物中多环芳烃的致癌性, 为大气颗粒物的防治提供参考依据, 减少多环芳烃对人类健康的影响 Fig. Figure title in English 图 结合随机森林和构效关系方法研究多环芳烃的致癌性的流程示意图 关键词 : 大气污染物 ; 多环芳烃 ; 致癌性 ; 定性构效关系 ; 随机森林 参考文献 []Yousefinejad, S.; Hemmateenejad, B.; Chemometr. Intell. Lab., 205, 49: 77. [2]Liaw, A.; Wiener, M.; R news, 2002, 2: 8. 本工作得到了科技部重大仪器设备开发专项 (No. 20YQ0303) 和国家自然科学基金 (No. 237505, 260523) 的支持 27

P-2-028 Surface-enhanced Raman spectroscopy based on Au-core/Ag-shell nanoparticles with embedded internal standard to quantify methimazole with Advanced Chemometric Method Xue-Qin Zhang, Chen*, Zuo 2 College of Chemistry and Chemical Engineering, Hunan University, Yuelu District, Changsha, 40082 2 College of Chemistry and Chemical Engineering, Hunan University, Yuelu District, Changsha, 40082 *Email: zpchen2002@hotmail.com (Z.P. Chen) Methimazole is widely used for various types of hyperthyroidism by preventing peroxidase. In this paper, the multiplicative effects model for surface-enhanced Raman spectroscopy (MEMSERS) combined with Au-core/Ag-shell nanoparticles with embedded internal standards (IS) was proposed for quantitative SERS assays of methimazole in the plasma and tablet. The core-shell nanoparticles with embedded IS have some advantages: IS molecule embedded inside the core-shell structure can t be influenced by the microenvironment to avoid dynamic dissociation, also, the target analytes completely occupy the adsorption site without competition of IS to effectively improve sensitivity. The corresponding average relative prediction error (ARPE) and root-mean-square error of prediction (RMSEP) values by using MEMSERS were 4.9%, 0.0 μm, respectively, far less than that of PLS, which proved that MEMSERS could effectively eliminate the adverse effects caused by SERS enhancing substrates, integrated instrument response, the change of focal position on SERS signals. MEMSERS provided more satisfactory quantitative results for methimazole in the plasma with the recovery rate mostly at 9.3%~02.% than the result of PLS. Also, MEM SERS model could accurately predict methimazole in tablet in accordance with specification, and the recoveries rates were between 99.6% ~ 05.7%. Detection limit was estimated to be 23.3 nm. Moreover, the advantages of good performance and simple implementation render MEMSERS model based on Au-core/Ag-shell nanoparticles potential and alternative tool in quantitative SERS assays of small molecules in many applications. Figure.the principle of experiment for detection of methimazole based on Au @ 4-MBA @ Ag Keywords: Surface-enhanced Raman spectroscopy; Methimazole; Au-core/Ag-shell nanoparticles; Embedded internal standard; Multiplicative effects model References: [] Zhou, Y.; Ding, R.; Joshi, P. Analytica chimica acta. 205, 874: 49-53. [2] Shen, W.; Lin, X.; Jiang, C. Angewandte Chemie International Edition. 205, 54(25): 7308-732. 272

P-2-029 Chemometrics-enhanced HPLC-DAD strategy for rapid quantification of seven nitroaromatic compounds in environmental water samples Yihuan Zhao, Jianfang Chen, Menglong Li,Xuemei Pu,* College of Chemistry, Sichuan University, Chengdu, 60064 *Email: xmpuscu@scu.edu.cn Nitroaromatic compounds pose a significant risk to human health and other living organisms. However, the conventionally high performance liquid chromatography (HPLC) methods are complicated and time-consuming for complete separations of multiple nitroaromatic compounds due to their high structure-similarities. In the work, a facile yet effective strategy of utilizing HPLC embedded bydiode array detection (HPLC-DAD) combined with one second-order calibration algorithm (MCR-ALS) was proposed to improve the HPLC analysis, through which seven nitroaromatic compounds with similar structures could be rapidly quantified under a simple isocratic elution condition (acetonitrile/water: 65:35, v/v) within 0 min. Despite of significant overlaps of some peaks and the presence of unexpected interferences from the real water sample, acceptable quantification results were still achieved with the aid of the second-order advantage. Elliptical joint confidence region (EJCR) tests further confirm that the proposed method has no proportional and constant error in the predicted concentrations. Thus, the combination of the HPLC method and the second-order calibration algorithm has high potential to be a simple, quick and accurate method for simultaneous determination on multiple nitroacromatic compounds in practice. The strategy derived from our work could advance analytical methods in environmental monitoring and the other complicated systems with multiple components. Keywords: Nitroaromatic compounds; MCR-ALS; Environmental water; High performance liquid chromatography-diode array detection References: [] Yi, J., Xiong, Y., Xu, T., M, L., Pu, X. M.*. Sci. Rep. 206,6:9364. [2] Lu, T., Yuan, Y., Jiao, Y., Pu, X. M.*. Chemometr. Intell. Lab. 206,54:72-79. [3] Lu, T., Yuan, Y., He, X., Li, M. L., Pu, X. M.*. Rsc. Adv. 205, 5(7):302-3027. [4] Lu T, Wen Z, Wang L, Pu, X. M.*. Chemometr. Intell. Lab. 205, 47:3-38. 273

P-2-030 Bagging Classification Tree-Based Robust Variable Selection for Radial Basis Function Network in Metabonomics Data Analysis Hui Gu, Meng-Ying Tu, Yan-Ping Zhou * College of Chemistry, Central China Normal University, Wuhan, 430079 *Email: hgzyp@mail.ccnu.edu.cn One main goal of chemometrics in metabonomics is to identify some informative variables so as to discover the potential biomarkers, since biomarkers can be of great importance for either biological or clinical purpose. Usually, the informative variables are determined by firstly establishing a classifier with reasonable recognition capacity followed by measuring the variable contribution to inter-group differentiation. However, the situation that the informative variables are elicited from a single model may lead to some uncertainty. To overcome this issue, in the current study, inspired by the characteristic of CT in automatically selecting the most variables, the potential of bagging in improving the reliability and robustness of a single model, and the promising modeling performance of radial basis function network (RBFN), we designed a new chemometrics tool abbreviated as BAGCT-RBFN for metabonomics data analysis. In BAGCT-RBFN, a series of parallel CT models were firstly established based on the idea of bagging (BAGCT). Then, RBFN was utilized to relate all the splitting variables involved in BAGCT and the classification memberships. A H NMR-based metabonomics data associated lung cancer was applied to test the performance of BAGCT-RBFN. The results showed that BAGCT-RBFN with fewer variables compares favorably with CT as well as RBFN. In addition, several most discriminative metabolites were identified by BAGCT-RBFN to aid the diagnosis of lung cancer with reliability, including lactate, choline, myo-inositol, trimethylamine, dimethylamine, proline, threonine, and lipid. Table. Classification results by using BAGCT-RBFN compared with those obtained by CT and RBFN. Data set RRtotal RRtotal RRtotal BAGCT-RBFN RBFN CT Training set 93.65% 93.65% 93.65% Test set 86.96% 78.26% 65.22% Fig. Basic idea of BAGCT-RBFN Keywords: chemometrics; metabonomics; bagging classification tree-radial basis function network (BAGCT-RBFN) References: [] Jansen, R.S.; Rhee, K.Y. Trends Pharmacol. Sci. 207, 38(4), 393-405. [2] Jung, Y.S.; Jueun, L.; Jungju, S.; Geum S.H.; Environ. Toxical. 207, 32(4), 262-272. Acknowledgements We are grateful to the national natural science foundation of China (2675059), the self-determined research funds of CCNU from the colleges' basic research and operation of MOE (No. CCNU6A05006). 274

P-2-03 独立成分分析应用于温控近红外光谱数据的研究朱雪薇, 蔡文生, 邵学广 * 南开大学化学学院, 分析科学研究中心, 天津市卫津路 94 号,30007 *Email: xshao@nankai.edu.cn 近红外光谱体现了分子内和分子间相互作用的信息, 温度的变化会影响分子内和分子间的相互作用信息, 导致物质结构的转变, 从而温度的变化会引起近红外光谱的变化 因此可以利用近红外光谱的温度效应对物质结构进行研究 [-3] 本课题组利用温控近红外光谱技术对 N- 甲基乙酰胺水溶液中的结构变化进行研究 在不同温度下采集不同浓度的 NMA 水溶液的近红外光谱 多组分吸收峰的重叠导致无法直接从光谱中分析 NMA 水溶液中的结构和氢键变化 因此采用独立成分分析 (ICA) 的方法从近红外光谱中提取纯组分的光谱信息, 得到五个独立成分及相应的混合矩阵, 将五个独立成分分别归属为不同大小的水团簇 (S0 S 和 S2) H + (H2O)2 和 NMA 为考察温度和浓度扰动对 NMA 水溶液的影响, 通过计算得到混合矩阵和独立成分的重构组分 发现温度会引起 NMA 的结构变化 NMA 浓度的增加使得水分子的氢键网络被严重破坏, 同时,NMA 自缔合程度增加 此外, 本课题组还利用 ICA 在重叠信号解析方面的优势, 对三种脂肪伯胺 ( 正戊胺 正己胺 正庚胺 ) 温控近红外光谱数据进行分析, 对分子间氢键作用形式进行研究 ICA 结果得到了脂肪伯胺分子间 NH 基团的三种存在形式, 分别是自由 线型键合和环状键合的 NH 基团 对比三种脂肪伯胺近红外光谱温度效应的 ICA 结果发现, 随着侧链碳链长度的增加, 键合形式的 NH 基团受温度影响减弱 其中, 线型键合形式受空间位阻效应的影响最大 关键词 : 近红外光谱 ; 温度效应 ; 独立成分分析 ; 物质结构 参考文献 [] Qi, L.-H.; Cai, W.-S.; Shao, X.-G. Acta Chim. Sinica 206, 74:72. [2] Cui, X.-Y.; Cai, W.-S.; Shao, X.-G.; RSC Adv. 206,6:05729. [3] Cui, X.-Y.; Liu, X.-W.; Yu, X.-M.; Cai, W.-S.; Shao, X.-G.; Anal. Chim. Acta 207,957:47. 国家自然科学基金项目 (No. 2475068) 资助 275

P-2-032 Quantitative analysis of enantiomers by multiplicative effects model and liquid chromatography-mass spectrometry Yan-Li Zhu, Chen*, Wang 2 College of Chemistry and Chemical Engineering, Hunan University, Yuelu District, Changsha, 40082 2 College of Chemistry and Chemical Engineering, Hunan University, Yuelu District, Changsha, 40082 *Email: zpchen2002@hotmail.com (Z.P. Chen) A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method combined with mass spectrometry multiplicative effects model (MEMMS) for high-sensitivity quantitative analysis of chiral propranolol compounds was conducted. The method was based on a chemical derivation process that applies a simple chiralchloride reagentas the probe.the resulting diastereomers were successfully recognized without any Column,the information of the abundance of the fragments was detected by mass spectrometry multiple reaction monitoring (MRM) and was used to process by the multiplicative effect model.experimental results showed that MEMMS can provide quite precise concentation predictions for enantiomers of propranolol in turbid media with an average relative error of about 2%, the method achieves a ower limit of quantification of 50 pmol, mean recoveries of the pharmaceuticals ranged from 97 to 06%, the APRE of the model was.2 %. Thus, the present method can be demonstrated as a new and practical technique of rapidly and sensitively determining enantiomers of propranolol hydrochloride tablets. Figure.the principle of experiment for detection of enantiomers of propranolol based on HPLC-MS /MS Keywords: HPLC-MS /MS; Chiral propranolol; Multiplicative effects model References: [] L. Wang, Y.F. Chai, Z.Q. Ni, L. Wang, R.L. Hu, Y.J. Pan, C.R. Sun, Qualitative and quantitative analysis of enantiomers by mass spectrometry: application of a simple chiral chloride probe via rapid in-situ reaction, Anal. Chim. Acta 809 (204) 04 08. 276

通过温控近红外光谱及水光谱组学研究 DNA 构象的变化 * 王利, 马丽, 蔡文生, 邵学广 南开大学化学学院, 分析科学研究中心, 天津市卫津路 94 号,30007 *Email: xshao@nankai.edu.cn 温控近红外光谱技术在生物分子结构研究方面有着独特的优势, 在温度的扰动下, 物质结构的振动容易受到影响, 这种结构变化必然会引起近红外光谱的改变, 因此利用温控近红外光谱可以获取物质结构的信息 并且水光谱组学的提出为生物分子结构的分析提供了新思路 [], 通过研究水和近红外光的相互作用可以获取水结构的信息以及生物分子结构的信息 本课题组将温控近红外光谱和水光谱组学相结合, 研究了生物分子如葡萄糖 [2,3] 蛋白质[4] 等与水之间的相互作用, 通过分析水的谱峰变化来反映物质的结构变化 本研究旨在利用温控近红外光谱及水光谱组学研究 DNA 构象的变化, 先通过差谱分析了 DNA 构象随温度的变化, 然后通过主成分分析分析了 DNA 构象的变化对水结构的影响 结果表明, 低温时 DNA 主要呈现有序的碱基堆积构象, 高温时主要呈现无规卷曲构象 另一方面,DNA 溶液中的水分子随温度的变化呈现曲线趋势, 低温时变化较大, 高温时变化较小, 这种结构的变化可以反映 DNA 构象的变化 并且 DNA 溶液中的水团簇连接增强, 说明了 DNA 的水化层结构可能更加有序 关键词 : 近红外光谱 ; 温度 ;DNA; 构象的变化 ; 水光谱组学参考文献 [] Tsenkova, R. J. Near. Infrared. Spec.2007, 8: 4 [2] Cui, X.Y.; Cai, W.S.; Shao, X.G. RSC Adv. 206, 6: 05729. [3] Cui, X.Y.; Liu, X.W.; Yu, X.M.; Cai, W.S.; Shao, X.G. Anal. Chim. Acta 207, 957: 47. [4] Fan, M.L.; Cai, W.S.; Shao, X.G. Appl. Spectrosc. 207, 7:472. 国家自然科学基金项目 (No. 2475068) 资助 277

P-3-00 Understanding Structural Properties and Vibrational Spectra of Ethylammonium Nitrate Ionic Liquid Confined in TiO2 slits: The role of Hydrogen Bond Zhongyang Dai, Linghong Lu,* Ziqian Tang, Lili Shi, Shanshan Wang, Xinyi Song College of Chemistry and Chemical Engineering, State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing Tech University, 5 Xinmofan Road, Nanjing, 20009, PR China ABSTRACT: The structures and relevant vibrational spectra of an ethylammonium nitrate (EAN) ionic liquid (IL) confined in TiO2 slits with various slit sizes have been investigated in detail by using classical molecular dynamics simulation. Our simulation results demonstrate that the EAN IL confined in larger TiO2 slits can form double peaks structure of CH3 group for the EA + cations, and the peaks for the NH3 + group of cation and NO3 - anion occur in the almost same position, near the TiO2 wall. However, in the 0.7 nm TiO2 slit, the ordered single peak structure of CH3 group for EA + cation have been found, and the NH3 + groups of cation refer to cling to the surface of TiO2 walls compared NO3 - anion. For the cations confined in TiO2 slits, the NH3 + groups stay closer to the TiO2 walls because of the TiO2 hydrophilic nature, while the CH3 groups tend to point toward the opposite. Accordingly, the NO3 - anions prefer to tilted along the TiO2 surface with the N atoms facing the TiO2 walls to form hydrogen bonds (HBs) with the NH3 + groups. In additions, in the 0.7 nm TiO2 slit, for the NH3 + groups of cation, the N-H symmetric stretching mode almost disappears, and the N-H asymmetric stretching mode is split into two characteristic peaks with one peak appearing at a lower frequency. The disappearance is attributed to almost all NH3 + groups involving in forming the HBs, due to the enhanced confinement in 0.7 nm TiO2 slit. And the splitting phenomenon is due to the prominent HBs strength between the cations and TiO2 wall, which decay the vibration frequency of N-H stretching mode, dramatically. For the anions confined in the larger TiO2 slits, the N-O stretching mode has a slight red shift with respect to the bulk value, which is attributed to the enhanced HBs proportion between anions and cations. 278

P-3-002 Flow-Induced Polymer Translocation through a Nanopore from a Confining Nanotube Mingming Ding and Tongfei Shi * State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 30022 *Email: tfshi@ciac.ac.cn The flow-induced polymer translocation across a membrane through a nanopore has been the subject of much recent study due to its importance in biological systems and emerging nanotechnologies based on the macromolecule filtering. The theoretical studies on the flow-induced polymer translocation through nanopores have mainly focused on the confinement in laterally unbounded spaces between flat walls. However, in reality, the double-layer membrane is extensively used in experiments for the polymer translocation. Based on our previous work, we study the flow-induced polymer translocation through a nanopore from a confining nanotube, using a hybrid simulation method that couples point particles into a fluctuating lattice-boltzmann fluid. Our simulation illustrates that the critical velocity flux of the polymer linearly decreases with the decrease in the size of the confining nanotube, which corresponds well with our theoretical analysis based on the blob model of the polymer translocation, i.e., Jc~Jc,0D/L (as shown in Fig.). In addition, by decreasing the size of the confining nanotube, we find a significantly favorable capture of the polymer near its ends, as well as a longer translocation time. Our results provide the computational and theoretical support for the development of nanotechnologies based on the ultrafiltration and single-molecule sequencing. Fig. Schematic representation for the initial conformation of the polymer in the flow-induced translocation through a nanopore from a confining nanotube. The inset shows the critical velocity flux (J c) as a function of the size of the confining nanotube (D/R g0). Keywords: polymer translocation; flow-induced; nanopore References: [] De Gennes, P. Adv. Polym. Sci. 999, 38: 9. [2] Jin, F.; Wu, C. Phys. Rev. Lett. 2006, 96: 23780. [3] Ding, M.; Chen, Q.; Duan, X.; Shi, T. J. Chem. Phys. 206, 44: 74903. 279

P-3-003 Theoretical design and computational screening of precursors for atomic layer deposition Guoyong Fang* College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035 *Email: fanggy@wzu.edu.cn An effective precursor is a prerequisite and key to the success of ALD. Currently, the design of more effective precursors is an important aspect of the development of ALD technology. Theoretical design and computational screening methods for ALD precursors are discussed. Theoretical calculations can predict many properties of precursors, such as the bond strength between the metal and the ligand, the thermolysis energy and barrier, the chelation energy, the hydrolysis energy, the formation energy, and so on. Most of these calculated data are related to the stability and reactivity of the precursor, which can be used in the design and computational screening of new ALD precursors. In addition, precursor design and screening require consideration of the ALD reaction mechanism in order to predict the true reactivity of the precursor with the surface, namely the surface reactivity of the precursor, which reflects the essence of ALD technology. Such theoretical efforts are expected to provide guidance for the design of more effective precursors and thereby lead to an improvement of ALD applications. Fig. Theoretical design and computational screening for ALD precursors Keywords: atomic layer deposition (ALD); computational screening References [] Klaus, J. W.; Sneh, O.; George, S. M. Science 997, 278, 934-936. [2] Ritala, M.; Kukli, K.; Rahtu, A.; Räisänen, P. I.; Leskelä, M.; Sajavaara, T.; Keinonen, J. Science 2000, 288, 39-32. [3] Hausmann, D.; Becker, J.; Wang, S.; Gordon, R. G. Science 2002, 298, 402-406. [4] Fang, G.; Chen, S.; Li, A.; Ma, J. J. Phys. Chem. C 202, 6, 26436-26448. [5] Fang, G.; Ma, J. Nanoscale 203, 5, 856-869. [6] Fang, G.-Y.; Xu, L.-N.; Cao, Y.-Q.; Wang, L.-G.; Wu, D.; Li, A.-D. Chem. Commun. 205, 5, 34-344. [7] Xu, L.; Fang, G.; Cao, Y.; Li, A. Phys. Chem. Chem. Phys. 206, 8, 3223-3229. [8] Fang, G.; Xu, L.; Ma, J.; Li, A. Chem. Mater. 206, 28, 247-255. [9] Fang, G.; Xu, L.; Cao, Y.; Li, A. Coord. Chem. Rev. 206, 322, 94-03. 280

P-3-004 拉伸诱导结晶中的支化链作用关鑫超, 吴一弦 2, 胡文兵, * 南京大学化学化工学院高分子系, 配位化学国家重点实验室, 南京,20023 2 北京化工大学, 化学能源工程国家重点实验室, 北京,00029 *Email: wbhu@nju.edu.cn 实验研究发现, 支化链的引入对于结晶过程具有阻碍作用 [-2] 我们利用动态蒙特卡洛模拟方法 [3-5] 对拉伸诱导支化高分子结晶中支化链数目 链长和分布的影响做了系统的研究 研究发现, 支化链数目对结晶过程的影响比支化链链长的影响更为明显 相比于随机分布的支化链, 等间距分布的支化链的结晶起始点更低 然后我们把线形链和支化链按照不同摩尔分数共混, 研究共混物的拉伸诱导结晶 发现体系中线形链的含量越高, 拉伸起始点越低, 即成核过程主要由线形链驱动, 且拉伸过程中无明显的相分离 关键词 : 蒙特卡洛模拟 ; 拉伸诱导结晶 ; 支化链数目和链长 ; 阻碍作用 ; 线形链支化链共混 参考文献 [] Alamo, RG.; Domszy, R.; Mandelkern, L. J. Phys. Chem. 984, 88: 6587. [2] Alamo, RG.; Mandelkern, L. Macromolecules. 989, 22:273. [3] Nie, YJ.; Gao, HH.; Yu, MH.; Hu, ZM.; Reiter, G.; Hu, WB. Polymer. 203, 54: 3402-3407. [4] Nie, YJ.; Gao, HH.; Wu, YX.; Hu, WB. Soft Matter. 204, 0: 343-347. [5] Nie, YJ.; Gao, HH.; Hu, WB. Polymer. 204, 55: 267-272. 致谢本工作得到国家自然科学基金委 (No. 227406, 2474050) 的资助! 28

P-3-005 通过分子模拟研究水在不同二维材料中的传递性质 * 宋新毅, 吕玲红, 魏明杰, 王珊珊 南京工业大学化学工程与工艺学院材料化学重点实验室, 江苏省南京市鼓楼区新模范马路 5 号,20009 *Email: linghonglu@njtech.edu.cn 摘要近年来, 二维材料在海水淡化, 提高水通量和离子截留等方面有着非常重要的贡献 不同二维材料中水的通量并不相同,Grossman 等人 [] 通过对石墨烯多孔参料的模拟发现, 板间距, 孔之间的距离, 孔径的大小都对水的通量有很大的影响 而最近因为 N.R. Aluru 等人 [2] 发现 MoS2 是一种新型的具有高通量和选择性的二维膜材料而受到大量的研究 膜过程通常借助压差, 电势差或化学位差, 推动物质发生由低位向高位的流动 基于此, 本文试图通过非平衡分子动力学的方法研究不同膜材料 (Graphene,hBN,MoS2) 的对水通量的影响, 并且同时考察板之间距离 (.5-5nm) 研究发现, 不同材质材料的化学性质, 将会对水通量的产生非常大影响, 板间距的改变也会使水在板间的流动发生显著改变 本文从密度分布, 速度分布, 传递系数来解释产生这种效应的原因 关键词 : 二维材料 ; 膜分离 ; 水通量 参考文献 : [] Cohen-Tanugi, D.; Lin, L.-C.; Grossman, J. C. Nano. Letters. 206, 6, (2), 027-033. [2] Mohammad H.; Amir B. F.; Narayana R. A. Nat. Commun. 205, 6:866 282

P-3-006 负载离子液体吸收二氧化碳的分子动力学模拟研究汤子仟, 吕玲红 2,*, 戴中洋 3, 谢文龙 4, 石丽丽 5, 陆小华 6 南京工业大学化工学院, 材料化学工程国家重点实验室, 南京,20009 *Email: :linghonglu@njtech.edu.cn 基于之前实验研究的结果, 我们利用分子动力学模拟研究了金红石负载的离子液体 ([hmim][tf2n]) 在不同担载厚度下吸收二氧化碳的结构 分布和扩散性质的变化, 同时将离子液体分别担载在氧化钛和石墨表面, 以研究不同固体表面的性质对于其吸收二氧化碳性能的影响 研究结果表明, 随着担载离子液体厚度的减小, 离子液体和二氧化碳的扩散系数相应的变大, 对于二氧化碳的吸收容量也相应增加 除此之外, 随着担载离子液体厚度减小, 更多的二氧化碳分子吸附在氧化钛表面 对于相同厚度的离子液体, 担载在石墨表面的离子液体的扩散系数大于担载在氧化钛表面的离子液体, 且担载在石墨表面的离子液体的扩散系数比不担载的离子液体的扩散系数大 在相同担载厚度下, 担载在氧化钛表面的离子液体对二氧化碳的吸收容量要比担载在石墨表面和没有担载的离子液体的大 通过本文的研究工作, 我们不但发现负载离子液体的厚度对于其吸收二氧化碳性能的重要影响, 同时也发现液固界面的相互作用显著影响离子液体在固体表面的分布 我们期望通过本文模拟研究结果探索负载离子液体吸收二氧化碳的微观机理, 而这些微观机理通过宏观实验通常是难以得到的 Fig. Solubility of CO 2 in immobilized IL and self-diffusion coefficients of CO 2 in immobilized IL. 关键词 : 二氧化碳 ; 吸收 ; 离子液体 ; 界面 283

P-3-007 The chain-growth of Ammoniaborane: The mechanism Study of the Dehydrogenation of a Traditional Lewis Pairs Catalyzed by Frustrated Lewis Pairs Kun Wang,2, Jian-Guo Zhang 2 Department of Chemistry, Anhui University, Hefei, Anhui, 23060 2 State Key Laboratory of Explosion Science and Technology, Beijing Institute of Technology,0008 *wangkun@ahu.edu.cn Ammonia borane (AB)as an outstanding hydrogen-storage material has been gained a lot of attentions. It can be regenerated from polyborazylene (PB) but the uncontrollable dehydro-coupling in the polymerization from AB to PB is still a problem for the continuous application of AB. Frustrated Lewis Pairs (FLPs) is a landmark discovery to dissociate small molecules by activating strong nonpolar bonds reversibly without any metals. Here we analysis the interaction between AB and a dimethylxanthene-derived FLPs based on the experiments, which is also a reaction between a traditional Lewis Pairs and a Frustrated Lewis Pairs. The kinetic and thermodynamic properties of the catalysis process are calculated under M062X/cc-pVTZ level and verified by mp2/6-3++g(3d,2p). The activation of B-H bondis the general fate-determining intermediates of the chain-growth process. The mechanism also give a clue of the possible reversibility of the dehydrogenation of AB. Fig. The reversible dehydrogenation of AB catalysed by dimethylxanthene-derived FLP (P ). Keywords: Frustrated Lewis Pairs (FLPs); Metal free hydrogenation; Hydrogen-Storage material; Density functional theory References: [] Mo, Z. B.; Pit, A.; Campos, J.; Kolychev, E. L.; Aldridge, S. J. Am. Chem. Soc. 206, 38: 3306. [2] Stephan, D. W. Science 206, 354:248. [3] Welch, G. C.; Juan, R. R. S.; Masuda, J. D.; Stephan, D. W. Science 2006, 34: 24. 284

P-3-008 HIV- 蛋白酶构象变化机制及抗药性突变的影响于玉琪,, 王进安,, 陈照强, 王桂敏, 邵强,*, 施继晔 2,*, 朱维良,* 中国科学院上海药物研究所新药研究国家重点实验室药物发现与设计中心, 上海市祖冲路 555 号,20203 2 UCB Biopharma SPRL, Chemin du Foriest, Braine-l'Alleud, Belgium, 420 *Email: qshao@mail.shcnc.ac.cn HIV- 蛋白酶是一个重要的药物靶标 蛋白酶从闭合到张开的构象变化主要集中于 flap 区域, 其动态变化对底物结合至关重要 采用显 / 隐性混合溶剂模型副本交换方法 (hremd)[], 我们成功捕捉到已解析晶体结构中的闭合和半张开状态, 还发现了一个介于闭合和半张开状态的中间态 :curled 状态 通过绘制蛋白酶构象变化的自由能图景, 我们描绘了蛋白酶完整的构象变化过程 : 闭合 curled 半张开 全张开 与此同时, 为了研究抗药性突变对蛋白酶及蛋白酶 - 抑制剂复合物结构柔性的影响, 我们用常规的动力学模拟研究了野生型蛋白酶及 Flap+( L0I/G48V/I54V/V82A) Act(V82T/I84V) 两个突变体及他们分别与 Amprenavir 和 Darunavir 两种抑制剂的复合物 [2] 对比发现蛋白酶的 80s (80 s) loop 与 flap 区域存在强疏水作用稳定 flap 的闭合状态, Act 突变减弱了疏水作用, 从而导致蛋白酶的 flap 区域更容易过渡到半张开构象 对应的, Act 突变的蛋白酶 - 抑制剂复合物内, 抑制剂疏水团与 flap 区域的 I50(I50 ) 和 80s(80 s) loop 区域的 I84(I84 ) V82(V82 ) 疏水簇作用减弱, 使 flap 区域柔性增大, 从而赋予其更强抗药性 [3] 关键词 :HIV- 蛋白酶 ; 显 / 隐性混合溶剂模型副本交换 ; 抗药性 参考文献 [] Wang, J.; Zhu, W.; Li, G.; Hansmann, U.H.E. J. Chem. Phys. 20, 35: 0845. [2] Yu, Y.; Wang, J.; Shao, Q.; Shi, J.; Zhu, W. Sci. Rep-UK. 205, 5: 057. [3] King, N. et al. 202, 7: 536. HIV- Protease Flap Opening Transition and the Effects from Drug-resistant mutations Yuqi Yu,, J. Wang,, Z. Chen, G. Wang, Q. Shao,*, J. Shi 2,*, W. Zhu,* Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 20203 2 UCB Biopharma SPRL, Chemin du Foriest, Braine-l'Alleud, Belgium *Email: qshao@mail.shcnc.ac.cn HIV- protease (PR) is an effective drug target for antiviral inhibitors. The conformational dynamics in the flaps plays a crucial role in substrate binding process. Using hybrid explicit/implicit solvent REMD, we characterized important intermediate states of the flap opening transition. The observation of the curled intermediate state helps to provide an integrated view of the transition pathway of the flap opening of HIV- PR (closed curled semi-open fully open). Moreover, to investigate drug-resistant mutations effect on the dynamic properties of HIV- PR, we simulated wild-type, Flap + (L0I/G48V/I54V/V82A) and Act (V82T/I84V) variants as well as their complexes with Amprenavir and Darunavir inhibitors using conventional molecular dynamics. The hydrophobic interactions between flap and 80 s (80 s) loop residues (mainly I50-I84 and I50 -I84) helps to stabilize the closed state. The hydrophobic clusters created by inhibitor, flaps and 80s loop play a crucial role in stabilizing the closed conformation of flaps. Keywords: HIV- protease; explicit/implicit hybrid REMD; multi-drug resistance 285

P-3-009 基于碳纳米管 - 嗅觉受体生物传感器的分子设计和理论研究张力耘, 沈鑫, 李庆悦, 李梦龙, 蒲雪梅,* 四川大学化学学院, 四川, 成都,60064 *Email: xmpuscu@scu.edu.cn 基于嗅觉受体的生物电子鼻是一类新型的生物亲和气味分子性传感器, 建立在嗅觉受体与气味分子的特异性结合的基础上, 在食品 环境 医药 军事等领域有着广泛的应用前景 纳米粒子作为嗅觉受体的固定材料和基础电极的修饰材料会对蛋白结构和底物识别能力造成一定改变, 而这些在微观上影响生物传感器性能的因素在实验上很难捕捉, 因此, 我们结合分子动力学模拟以及虚拟筛选方法, 研究了单壁碳纳米管 (CNT) 固定化嗅觉受体过程中结构和功能的改变 动力学模拟结果表明, 嗅觉受体与 CNT 会发生快速 分步式的非特异性吸附作用, 虽然吸附过程会使受体胞内一些 loop 区结构发生变化, 但主要二级结构保留完整, 这也是受体保持活性的原因 对 32 个气味小分子虚拟筛选的结果表明,CNT 的固定化能够显著加强受体对小分子的亲和能力, 并且自由受体更加倾向结合大分子, 而 CNT 固定化的受体对于小分子的结合能力有更为显著的增强, 因为 CNT 可别构调节受体结合口袋体积, 改变了对配体的选择性 同时我们还发现自由受体和 CNT 固定化受体均对疏水性较强的小分子有较高亲和能力 这些研究结果可为基于 GPCR 生物传感器的优化设计和应用提供的理论指导 Fig. the CNT-immobilized olfactory receptor with an odor molecule (left), and the variation of binding energy score along with molecular weight from the virtual screening of 32 odor molecules (right) 关键词 :G 蛋白偶联受体 ; 嗅觉受体 ; 生物传感器 ; 碳纳米管 ; 分子动力学 参考文献 [] Zhang, L. Y.; Li,Y.Z.; et.al; Li, M. L.; Pu, X. M.*. Sci. Rep. 206, 6: 36838 [2] Zhang, L. Y.; Xiao, X. C.; et.al; Li, M. L.; Pu, X. M.*. Sci. Rep. 205, 5: 9297 [2] Zeng, X. J.; Zhang, L. Y.; et.al; Pu, X. M.*; Li, M. L.*. Sci. Rep. 206, 6, 24065 [3] Gao, N.; Liang, T.; et.al; Li, M. L.; Pu, X. M.*. Phys. Chem. Chem. Phys. 206, 8, 2942 286

P-4-00 Liquid Structure and Ion Formation in Magnesium Borohydride Electrolyte Joshua D. Deetz, Fenglei Cao, Qi Wang, Huai Sun* School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, 200240 *Email: huaisun@sjtu.edu.cn Rechargeable magnesium batteries have the capability to safely and cheaply store energy in an electrochemical form. Compared to lithium-ion batteries, magnesium batteries have several advantages, including: nearly double the volumetric capacity (3832 vs. 206 mah/cm 3 )[], safer operations, and lower cost. Recently, it was discovered that an electrolyte consisting of magnesium borohydride, Mg(BH4)2, and an ethereal solvent, could be used to as part of a rechargeable battery.[2] It has been hypothesized that some important properties of the electrolyte, such as the conductivity, and the degree of ion formation, depend on the properties of the solvent in the electrolyte.[3] In the present study, we use density functional theory to investigate the structure and energetics of neutral and charged ion-solvent clusters in electrolytes containing magnesium borohydride in tetrahydrofuran (THF), monoglyme (G), and diglyme (G2). Our calculations indicate that the free energy required to form a singly charged cation is lower in G than it is for THF or G2. Regardless of the solvent used, the free energy required to form cationic clusters is quite high. The concentration of these ions is expected to be low. By comparing theoretical vs. experimental FTIR spectra, the concentration of divalent cationic clusters in the electrolyte is predicted to be very low, which agrees with their high formation energies. Calculated 25 Mg-NMR spectra indicate that the chemical shift of magnesium depends upon the charge of the clusters, indicating that it could be a used as a descriptor of ion formation in the electrolyte. References: [] Mohtadi, R. & Mizuno, F. Beilstein journal of nanotechnology 204, 5: 29 3 [2] NuLi, Y., Yang, J., Li, Y. & Wang, J. Chemical Communications 200, 46: 3794-3796. [3] Shao, Yuyan, et al. Nano Energy 205, 2: 750-759. 287

P-4-002 The mechanism of Vismodegib inhibition of Smo was investigated by MetaD method Xiaoli An, Xiaojun Yao * State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000 *Email: xjyao@lzu.edu.cn The smoothened receptor (Smo) plays a key transducer in Hedgehog (Hh) signalling pathway and it has been regarded as an efficacious therapeutic target in basal cell carcinoma (BCC) and medulloblastoma (MB) []. Nevertheless, the resistance mutation and active Smo mutants have put forward the requirement of finding effective inhibitors or novel targets. Here, we performed metadynamics [2] of Smo bound with antagonist vismodegib and with agonist cholesterol, denoted as Smo-Vismod and Smo-CLR respectively, to explore their inhibition or activation mechanism. The simulation results indicated that the extracellular cysteine-rich domain (CRD) leans close to membrane plane in activated Smo-CLR. On contrarily, the CRD is far away from membrane plane in inhibited Smo-Vismod. Moreover, an open CRD groove conformation that has not been noticed in previous reports [3] was also observed in inhibited Smo-Vismod. The open CRD groove was occupied by helix Ⅵ and ECL3 which can be attribute to strong hydrophobic interactions among hydrophobic residues of CRD groove, hinge domain (HD), helix Ⅵ and extracellular loop3 (ECL3). As consequence, the occupied CRD groove prevents the binding of cholesterol and may also hold up the CRD stack atop the TMD. In addition, the HD and ECLs play crucial roles in coordinating their interaction with CRD and TMD. Meanwhile, the Vismod-induced shift of helices of TMD-site permits the helix Ⅵ entering CRD groove along with the ECL3. In the intracellular side, the movement of intracellular loops (ICLs) may potentially block downstream effectors contact. These results are expected to contribute to novel inhibitors discovery and novel targets illumination. Keywords: the smoothened receptor; metadynamics; vismodegib References: [] di Magliano, M. P.; Hebrok, M. Nat. Rev. Cancer. 2003, 3: 903-. [2] Laio, A.; Parrinello, M. Proc. Natl. Acad. Sci. U S A. 2002, 99: 2562-6. [3] Byrne, E.F.X.; Sircar, R.; Miller P. S.; Hedger, G.; Luchetti, G. Nature. 206, 535: 57-522. 288

P-4-003 单位点 DNA 甲基化对 C/EBPβ 转录因子与 DNA 特异性识别序列相互影响机制的分子动力模拟研究 别丽华, 杜利凯 2, 高军 * *Email: gaojun@mail.hzau.edu.cn DNA 甲基化在真核生物中广泛存在, 与细胞分化 胚胎发育 环境适应和疾病发生等各种功能相关, 是重要的表观遗传学标记, 也是当前表观遗传学研究的热点领域之一 研究表明,DNA 甲基化可以通过调控转录因子和 DNA 的结合特异性来发挥作用, 但是目前其分子机制尚不清楚 蛋白 - 核酸之间的相互作用是一个十分复杂的动态过程, 涉及蛋白互作,DNA 序列结构, 水分子及离子, 蛋白 - 核酸之间的相互作用等多个层面, 采用分子动力学模拟方法在解释蛋白核酸相互作用的分子机制方面有一定的优势 我们以 bzip 转录因子家族 C/EBPβ 蛋白为研究对象, 从高精度晶体结构出发, 采用分子动力学方法比较了单位点 DNA 甲基化前后蛋白核酸相互作用机制的区别, 发现氢键和局域静电相互作用的变化对蛋白核酸识别机制具有重要影响 甲基化位点可诱导增强蛋白侧链对甲基化位点的识别, 也进一步影响了与邻近碱基的堆积效应, 从而导致 DNA 碱基平面相对构象发生变化 对动力学轨迹的统计表明, 这一构象对堆积力的影响可沿着 DNA 骨架传递 本研究可进一步加深我们对蛋白核酸相互作用及其调控机制的理解 This work is supported by the National Natural Science Foundation of China (No. 237324) 289

P-4-004 原子团簇转变拓扑图的表征 蔡引江, 程龙玖 * 安徽大学化学化工学院, 合肥市九龙路 号,23060 *Email: clj@ustc.edu 原子团簇是由一定数目原子相互作用形成的稳态聚集体 原子团簇的数目和结构直接影响其物理性质和化学性质 对原子团簇结构和性质的研究以及预测不同数目下团簇的全局最优结构是各科研究领域中的热点, 反映原子团簇能量信息的势能图更是理解一些分子现象的重要关键 [] 本文在同一方法下, 通过对相同原子数目下不同结构团簇间转变的路径的表征, 来具体化出原子团簇的势能图 此外, 由团簇间转变拓扑图可以得出各结构间转变的最易转变路径, 从而有望根据已有的最优结构信息预测出较大数目下的团簇最优结构或者其结构类型范围 对于 38 原子团簇, 我们采用 Funnel hopping [2] 方法来进行优化 在优化过程中保留每次优化的前五个优解, 如此迭代至优化完成 通过记录下的每条优化路径信息我们可以得到此次优化中出现的各结构间的大致拓扑结构, 并用其绘制出拓扑路径图, 图 即为 38 原子团簇优化的拓扑路径图 图中各圆表示优化过程中出现的一种结构, 三角表示优化时的一系列结构 由图 中的局部最优解和全局最优解间的转变拓扑路径可以看出, 全局最优解作为一支较孤立分支验证了其结构较难找到的计算结果 同时, 在局部最优解之间存在着复杂的拓扑路径, 并且其中有着特征较为突出的拓扑节点 这些节点作为各局部最优解间转换路径中的能量最高点连接着大量的拓扑路径, 其对于团簇结构间的转变有着指向性的作用 关键词 : 原子团簇 ; 拓扑图 ; 势能面表征 Fig. Topological graph of 38-atoms-cluster 参考文献 [] Wales D, Miller M, Walsh T. NATURE. 998, 394(20): 758. [2] Cheng L, Feng Y, Yang J, Yang J. J. Chem. Phys. 2009, 30: 242. 290

P-4-005 扩展自适应偏置力方法在 PLUMED 中的实现 * 陈淏川, 邵学广, 蔡文生 南开大学化学学院, 分析科学研究中心, 天津市卫津路 94 号,30007 *Email: wscai@nankai.edu.cn 扩展自适应偏置力 (extended adaptive biasing force, 简称 eabf) [,2] 方法是一种重要性采样与自由能计算方法, 它利用扩展拉格朗日动力学改进了自适应偏置力 (adaptive biasing force, 简称 ABF) [3] 方法, 解决了原来 ABF 方法中反应坐标耦合与计算二阶导数的问题, 减少了反应坐标的使用限制并加快了计算收敛速度, 有一定的应用潜力, 但至今该方法只通过 Colvars [4] 模块在 NAMD [5] 和 LAMMPS [6] 中实现 PLUMED [7] 是一套可以和多种分子动力学模拟软件结合使用的自由能计算插件, 我们通过 PLUMED 插件实现 eabf 方法及相应的自由能估计量 (free energy estimator) [8,9], 使 eabf 方法可以在 Gromacs [0] 等分子动力学模拟程序中使用, 方便了 Gromacs 等程序的用户, 并且还可以使用 PLUMED 中一些独有的反应坐标, 扩大了 eabf 方法使用时反应坐标的选择空间 关键词 : 自由能计算 ; 重要性采样 ; 自适应偏置力方法 ;eabf;plumed 参考文献 [] Zheng, L.; Yang, W. J. Chem. Theory Comput. 202, 8(3): 80. [2] Lelièvre, T.; Rousset, M.; Stoltz, G. J. Chem. Phys. 2007, 26: 34. [3] Darve, E.; Pohorille, A. J. Chem. Phys. 200, 5: 969. [4] Fiorin, G.; Klein, M.; Hénin, J. Mol. Phys. 203, : 3345. [5] Phillips, J. C.; Braun, R.; Wang, W.; Gumbart, J.; Tajkhorshid, E.; Villa, E.; Chipot, C.;Skeel, L., R. D. Kalé; Schulten, K. J. Comput. Chem. 2005, 26: 78. [6] Plimpton, S. J. Comput. Phys. 995, 7:. [7] Tribello, G.; Bonomi, M.; Branduardi, D.; Camilloni, C.; Bussi, G. Comput. Phys. Commun. 204, 85: 604. [8] Fu, H.; Shao, X.; Chipot, C.; Cai, W. J. Chem. Theory Comput. 206, 2: 3506. [9] Lesage, A.; Lelièvre, T.; Stoltz, G.; Hénin, J. J. Phys. Chem. B 207, 2: 3676. [0] Hess, B.; Kutzner, C.; van der Spoel, D.; Lindahl, E. J. Chem. Theory Comput. 2008, 4: 435. * 本文系国家自然科学基金项目 (No. 23737) 资助 29

P-4-006 嵌段溶液亲疏水性对共聚物纤维晶体生长速率的影响 陈俊帆, 查利云, 胡文兵 * 南京大学化学化工学院高分子系, 配位化学国家重点实验室, 南京,20023 *Email: wbhu@nju.edu.cn 两嵌段共聚物在溶液中由结晶驱动的纳米纤维自组装动力学对我们理解纳米结构的调控具有重要意义 我们采用基于格子模型的动态蒙特卡洛分子模拟研究了两嵌段共聚物与溶剂间的亲疏水性对模板诱导的纤维状晶体生长速率的影响 我们分别固定结晶段和非晶段与溶剂间的相互作用参数, 改变另一参数, 再通过计算晶体胶束前沿的生长速率来比较其影响 我们发现, 当结晶段越疏水时, 晶体生长速率越快 反之, 非晶段越疏水时, 晶体生长速率越慢 针对这一现象, 我们认为, 结晶段与溶剂相互作用参数对晶体生长动力学的影响可以用热力学因素来解释, 而非晶段与溶剂相互作用参数的影响则可归因于非晶段的构象变化对晶体生长前沿的影响 我们的研究结果有助于我们采用改变嵌段选择性溶剂亲疏水性的办法来调控纳米纤维的生长动力学 关键词 : 纤维状晶体 ; 亲疏水性 ; 嵌段共聚物 ; 蒙特卡洛模拟致谢本工作得到国家自然科学基金委 (No. 2474050) 的资助! 参考文献 : [] Jeff Sevigny, Ping Chiao, Thierry Bussiere, et al. Nature, 206,537, 50-56. [2] Yujie Zhou, Wenbing Hu, J. Phys. Chem. B, 203, 7,3047-3053. [3] Shu R, Zha L, Eman A A, Wenbing Hu, J. Phys. Chem. B,205, 9(8):5926-32. 292

P-4-007 板状 蔻环衍生物电荷传输速率的量子化学计算 陈自然, 余文浩 2* 四川职业技术学院建筑与环境工程系, 四川遂宁,629000 2 四川师范大学化学与材料科学学院, 成都,60068 *Email: yuwenhao@sicnu.edu.cn 摘要 : 电荷传输速率是决定有机电子器件性能的关键参数之一 本文使用密度泛函理论, 在 M06-2X/6-3+G(d) 理论水平计算 9 个 板状 蔻类衍生物分子的电荷传输速率 结果显示 :9 个蔻类衍生物分子的能隙在 2.90 3.30 ev 范围, 归属于有机半导体 蔻环共轭面的大小对电荷传输性能影响较大, 在四苯并蔻 a 系和六苯并蔻 b 系分子的刚性核上引入甲基比引入甲氧基更有利于分子的空穴传输 在 长板状 的 c 系分子中, 引入甲氧基既有利于空穴传输, 也可增强电子传输性能, 可设计为双极性传输材料 蔻类衍生物是一类具有较高的本征迁移率, 可制造有机电子器件的稠环芳烃材料之一, 其中高有序柱状结构的六苯并蔻衍生物 (hexa-peri -hexabenzocoronenes, HBCs) 由 Mullen 和 Spiess 最先合成, 其电荷迁移率高达.0 cm 2 V - s - 最近蔻类的其他拓扑结构 - 四苯并蔻 (Tetrabenzo[a, d, j, m]coronene), 六苯并蔻 (Hexabenzo[a, d, g, j, m, p]coronenes) 衍生物也被合成, 其光电性能也得到了实验研究 量子化学计算可以预测新型稠环芳烃分子的电荷迁移速率, 从而指导进一步的实验研究 我们专注于使用 DFT 方法研究稠环芳烃的光电性能, 特别是盘状液晶半导体材料的电荷传输性能 目前量子化学计算主要集中在简单的圆盘状或三角状稠环芳烃分子的光电学能研究, 对于其他拓扑结构的稠环芳烃分子研究较少 使用 Gaussian 09 E.0 程序, 采用量子化学方法研究图 所示的 9 个 板状 蔻类衍生物分子的空穴与电子传输性能, 探讨了 板状 蔻类衍生物分子电荷传输性能与分子结构的关系 Fig. Molecular structures of coronene derivatives 关键词 : 有机半导体 ; 蔻类衍生物 ; 密度泛函理论 ; 载流子迁移率 ; 双极性传输 参考文献 [] Van, De, Craats, AM, Warman, JM, Fechtenkötter, A, Brand, JD, Harbison, MA, Müllen, K. Advanced Materials. 999, :469. [2] Warman JM, Kroeze JE, Schouten PG, van de Craats AM. Journal of Porphyrins and Phthalocyanines. 2003, 07:342. [3] Chen, Z, R, Yu, W, H. Molecular Physics. 207, 5:424. 293

P-4-008 DOX: 准确预测蛋白 - 配体结合构象的计算方法研究池波, 魏林, 任彦亮,*,* 2,*, 饶立, 万坚, 徐昕 华中师范大学化学学院, 武汉,430079 2 复旦大学化学系, 上海,200433 * Emails: jianwan@mail.ccnu.edu.cn;xxchem@fudan.edu.cn 蛋白质与配体的相互作用是生物体系分子识别 功能蛋白和调控酶发挥其生物功能的重要途径, 同时其相互作用机制是基于结构的药物设计的基础 近年来, 运用分子模拟方法理论预测蛋白 - 配体结合构象的方法较多, 其中分子对接以其快速高效的特点在分子模拟领域得到了广泛应用 分子对接方法被设计用于快速预测配体在蛋白结合位点中的结合模式及结合能力的强弱以实现大规模药物虚拟筛选, 也因此不免牺牲了预测结合模式的准确度 [] 随着计算机科学技术的发展, 基于高精度量子力学原理的量子化学方法被广泛应用在生物大分子体系的模拟中, 然而受其计算量所限, 量子化学方法无法直接应用于蛋白体系计算 [2] 为了准确预测蛋白 - 配体的结合构象, 同时平衡计算速度与精确度, 我们采用基于 MM/QM 多势能面 窜跃 的结合构象搜索与优化策略 (BC-SAMP) 来解决这一问题 我们基于 BC-SAMP 策略发展了一种进行蛋白 - 配体结合构象搜索及其低能构象优化的新方法 DOX [3-6] 为了测试 DOX 方法的准确性, 我们在多类蛋白药物复合物体系, 包含以氢键作用为主导的和以疏水作用为主导的体系进行了测试, 测试分别在原位对接 ( 对接配体构象来自晶体构象 ) 自对接 ( 对接配体构象为随机构象 ) 交叉对接 ( 对接配体构象为随机构象 ) 三个层次上进行 测试结果表明 DOX 方法在上述体系中均能准确预测出蛋白 - 配体结合构象的几何构型参数 关键词 : 分子对接 ; 蛋白 - 配体结合构象 ;BC-SAMP 策略 ;DOX 方法 参考文献 [] Plewczynski D.; Lazniewski M.; Augustyniak R.; Ginalski K. J. Comput. Chem. 20, 32:742. [2] Morokuma K. Philos. Trans. A. Math. Phys. Eng. Sci. 2002, 360:49. [3] Rao, L.; Chi, B.; Ren, Y.; Li, Y.; Xu, X.; Wan, J. J. Comput.Chem. 206, 37:336. [4] Jain A. N. J. Med. Chem. 2003, 46:499. [5] Stewart J. J. J. Mol. Model.203, 9:. [6] Guo W.; Wu A.; Xu X. Chem. Phys. Lett. 200, 498: 203. 294

P-4-009 润滑或粘滞? 水对于轮烷运动的作用 杜双利, 邵学广, 蔡文生 * 南开大学化学学院, 分析科学研究中心, 天津市卫津路 94 号,30007 *wscai@nankai.edu.cn 水作为一种常用的溶剂, 具有极性大, 强的氢键供 受体能力, 以及体积小等特点, 可以对大多数分子机器实现润滑作用 [], 这种作用也被认为是水作为 生命之源 的原因之一 [2] 然而, 在本研究中我们发现, 在某些情况下, 水也会对分子机器的运动起到粘滞作用 为了探究这个问题, 本文采用分子动力学模拟方法对图 中的轮烷进行研究, 结果表明 : 对于轮烷的穿梭运动, 水起到了润滑效果, 而对于轮烷的旋转运动, 水却起到了粘滞作用 为了探究这种作用机制的本质, 我们进行了能量分解, 结果表明, 对于由静电主导的穿梭运动, 水通过减弱链 - 环之间的静电吸引, 从而起到了加速的作用 ; 而对于由范德华主导的旋转运动, 水在几乎不改变范德华作用前提下, 减弱了推动旋转的静电力, 阻碍了轮烷的旋转 我们的工作深刻地解释了在分子机器中水的作用机制, 为新型分子机器的设计提供了理论指导 关键词 : 水 ; 润滑 ; 粘滞 ; 轮烷 图 : 本文所研究的轮烷 参考文献 [] Fu, H. H.; Shao, X. G.; Chipot, C.; Cai, W. S. Chem.Sci. 206, 8: 5087. [2] Barron, L. D.; Hecht, L.; Wilson, G. Biochemistry 997, 36: 343. 国家自然科学基金项目 (No. 23737) 资助 295

P-4-00 A DFT study on the mechanism of Rhodium-Catalyzed Regioselective Hydrothiolation of Allyl Amines Lin Feng, Baojing Zhou,* Computational Institute for Molecules and Materials, School of Chemical Engineering, Nanjing University of Science and Technology, Xiaolingwei 200, 20094 Nanjing, China. *Email: bzhou@mail.njust.edu.cn Hydrothiolation reactions play important roles in the synthesis of organosulfur compounds. We investigate the Rhodium-catalyzed hydrothiolation of allyl amines employing the bidentate phosphine ligands dppp with density functional theory (DFT) computations. The Markovnikov hydrothiolation pathways were compared with anti-markovnikov ones. Both hydrothiolation pathways consist of two elementary reactions, i. e., the Rh H insertion reaction, followed by C-S reductive elimination reaction to form the C S bond. The barrier heights for the two elementary reactions of the anti-markovnikov route are 5.0 kcal/mol and 0.7 kcal/mol, respectively; while those for the Markovnikov route are 8.6 kcal/mol and 8.0 kcal/mol, respectively. The rate of the second elementary step is lower, which is the rate-determining step of the reaction. Therefore, the Rhodium-catalyzed hydrothiolation of allyl amines employing dppp ligand prefers to adopt the anti-markovnikov manner to yield linear organic sulfides. Keywords: DFT; hydrothiolation; mechanism; allyl amines References: [] Jennifer L. Kennemur; Gregory D. Kortman; J. Am. Chem. Soc. 206, 38, 94 99. [2] Taichi Tamai; Akiya Ogawa; J. Org. Chem. 204, 79, 5028 5035. [3] Yong Yang; Robert M. Rioux; Green Chem. 204, 6, 396 3925. 296

P-4-0 水对轮烷穿梭运动的润滑作用 付浩浩, 邵学广, 蔡文生 * 南开大学化学学院, 分析科学研究中心, 天津市卫津路 94 号,30007 *wscai@nankai.edu.cn 采用分子动力学模拟和自由能计算方法研究了 Leigh 课题组合成的多氨基轮烷 [] 在乙醚, 乙腈, 乙醇和水中的穿梭运动 该轮烷的穿梭过程伴随着大环分子的构象变化和旋转 在非水溶剂中, 大环分子和链状分子形成的氢键是穿梭过程的主要驱动力, 而在水溶剂中, 疏水相互作用变为了主要驱动力, 并且轮烷穿梭的反应路径改变, 这种变化大大降低了轮烷穿梭过程的能垒, 加速了轮烷的穿梭运动 水的强极性, 同时作为氢键供体和受体的能力以及极小的体积是其能改变轮烷穿梭机理和加速穿梭运动的原因 这种水可以完全改变轮烷穿梭机理的性质将会对未来的分子机器设计提供新的思路 [2] 关键词 : 水 ; 润滑 ; 轮烷 ; 驱动力 图. Leigh 轮烷的结构 参考文献 [] Panman M. R., Bakker B. H., den Uyl D., et al. Nat. Chem., 203, 5: 929. [2] Fu H., Shao X., Chipot C., et al. Chem. Sci., 207, 8: 5087. 国家自然科学基金项目 (No. 23737) 资助 297

P-4-02 Simulation on tensile failure process of Irregular Nickel Nanorods based on the molecular dynamics method 方佳佳 刘玉河 张佳惠 傅应强 * 吴之传安徽工程大学生物与化学工程学院, 安徽, 芜湖,24000 Email:fyq@ahpu.edu.cn The tensile fracture failure behavior of two irregular Nickel nanorods with the middle parts strengthen or weaken were simulated based on molecular dynamics. Different system temperature, Stretching velocities and the size of strengthen or weaken parts with three crystal orientations of single crystals [00], [0] and [] were investigated respectively. All of the parameters that influence the tensile fracture failure behavior were discussed by the stress and the distribution of fracture position. The simulation results show that the fracture probability of the middle part becomes larger with the size of the middle parts smaller. The nanorods with different crystallographic orientations have different sensitivity to size. Tensile fracture became difficult when the middle parts strengthen properly. Fig. Schematic diagram of Nickel nanorods for simulation model Fig. 2 The stress with strain plots for different sizes Keywords:Molecular dynamics; strengthen; weaken References: [] F.Y. Wang, Y.Q. Fu, B.Z. Chi, Y.F. Dai, J.W. Zhao. Superlattices and Microstructures, 206.9.0,97: 94-03 [2] ]H.N.Wu, D.S. Xu, H.Wang, R. Yang. Journal of Materials Science & technology,206,32:033-042. * 国家自然科学基金项目 (240600); 安徽省大学生创新创业训练计划 (2050363057); 通讯作者 : 傅应强 298

P-4-03 Computer-aided Design of Organic Hole Transport Materials Yongliang Geng, Baojing Zhou,* Nanjing Univ Sci & Technol, Computat Inst Mol & Mat, Sch Chem Engn, Nanjing 20094, Jiangsu, Peoples R China. *Email: bzhou@mail.njust.edu.cn The storage and efficient conversion of energy is very important for modern society. Organic-inorganic perovskite solar cells (PSCs) based on organic hole transport materials (HTMs) have attracted wide interest due to their high power conversion efficiency which exceeds 20%. The hole transport layer is a key component of PSCs and is critical to improve the stability and energy conversion efficiency of the battery. Thus the performance of the HTMs filled in the hole transport layer is particularly important. The goal of this work is to design high quality HTMs. To achieve this goal, we calculate two properties, i.e. HOMO energy level and hole reorganization energy, of seven molecules based on electron transfer theory and first principles density functional theory in order to screen out the most appropriate molecule. We find TET is a particular promising molecule. Its HOMO energy level is -4.33 ev, while its hole reorganization energy is 3 mev. Both properties match the expected ideal values. Now TET is under synthesis for verification of its functions by an experimental group. Keywords: Organic hole transport material; Density functional theory (DFT); Hole reorganization energy; HOMO; TD-DFT References: [] Westheimer F H, Hager J E. The theory of the racem ization of optically active derivatives of diphenyl [J]. Chem Phys, 946, 4: 773. [2] Akihiro, K.; Kenjiro, T.; Yasuo, S.; Tsutomu, M., Organometal halide perovskites as visible-light sensitizers for photovoltaic cells. Journal of the American Chemical Society 2009, 3 (7), 6050-605. [3] HS, K.; CR, L.; JH, I.; KB, L.; T, M.; A, M.; SJ, M.; R, H.-B.; JH, Y.; JE, M.; M, G.; NG, P., Lead Iodide Perovskite Sensitized All-Solid-State Submicron Thin Film Mesoscopic Solar Cell with Efficiency Exceeding 9%. Scientific Reports 202, 2 (8). [4] Christians, J. A.; Fung, R. C. M.; Kamat, P. V., An inorganic hole conductor for organo-lead halide perovskite solar cells. Improved hole conductivity with copper iodide. Journal of the American Chemical Society 204, 36 (2), 758-764. 299

P-4-04 两种倍他司汀类药物分子结构与药理特性研究,2,2* 侯彦君, 蔡开聪 福建师范大学化学与材料学院, 福建福州,350007 2 福建省理论与计算化学重点实验室, 福建厦门,36005 *Email: ckc7@fjnu.edu.cn 人体前庭外周器官受损, 会导致眩晕 恶心 呕吐等症状, 这些症状通常会逐渐减轻, 这一自然恢复的过程称为前庭代偿 组胺 (HIS) 是参与前庭代偿的重要递质之一, 是 G 蛋白偶联受体 H 的弱激动剂,G 蛋白偶联受体 H3 的强拮抗剂 2,3 现阶段常用与组胺具有相同药理特性的盐酸倍他司汀 (BHD) 和甲磺酸倍他司汀 (BMT) 缩短前庭代偿时间, 促进机体恢复 为探究这两种药物在前庭代偿过程中与受体相互作用的机制, 我们在 B3LYP/6-3++G(d,p) 计算水平上将两种倍他司汀类药物和组胺进行结构优化, 同时将组胺 盐酸倍他司汀 甲磺酸倍他司汀优化后的结构分别与 H 和 H3 受体在 Discovery Studio 中进行分子刚性对接 4,5 ( 图 A) 利用 ZDock Score 以及配体与受体间可能形成的氢键判定对接难易程度和对接后复合物的稳定性 研究结果表明, 甲磺酸倍他司汀与 H H3 受体对接的 ZDock Score 分数最高 ( 分别为 7.6 和 7.7), 形成的氢键数最多 (8 个 ), 氢键距离最短 (2.3 Å); 盐酸倍他司汀 ZDock Score 分别为 5.6 和 5.7, 较前者略有逊色 ; 组胺最弱,ZDock Score 分别是 4.4 和 4.7 这两种倍他司汀类药物虽然均能促进前庭代偿的进程, 但成盐基团不同, 与受体相互作用的强弱有较大差别, 甲磺酸倍他司汀表现出更好的药效 研究结果为我们提供了一种探索药物与受体相互作用强弱 作用机制及预测药物疗效的有效手段 Fig. The preferred docking mode for BMT and H (panel A), and the relationship among Density and ZDock Score of different Clusters (panel B) 关键词 : 倍他司汀类药物 ;G 蛋白偶联受体 ; 分子对接 ; 量子化学计算 参考文献 [] Chong, R.; Berl, B.; Cook, B.; Turner, P.; Walker, K. Acta Neurol. Scand. 207, 35(6): 635. [2] Hu, W. W.; Chen, Z. Pharmacol. Ther. 207, 75: 6. [3] Mathews, M. A.; Camp, A. J.; Murray, A. J. Front Physiol. 207, 8:. [4] Subhashree, G. R.; Haribabu, J.; Saranya, S.; Yuvaraj, P.; Krishnan, D. A.; Karvembu, R.; Gayathri, D. J. Mol. Struct. 207, 45: 60. [5] Manivannan, M.; Rajeshwaran, K.; Govindhan, R.; Karthikeyan, B. J. Mol. Struct. 207, 44: 432. 300

P-4-05 可迁移的聚合物粗粒化力场开发黄灏, 吴量, 金钊, 曹风雷,, 孙淮 * 上海交通大学化学与化工学院上海 200240 *Email: huaisun@sjtu.edu.cn 粗粒化分子模拟是大尺度模拟高分子热力学和动力学行为的一种高效的研究方法 [] 开发建立系统性的高分子和聚合物的粗粒化力场是高分子模拟的基础性工作 同时温度迁移性也是高分子粗粒化力场亟需解决的问题 本文采用综合的粗粒化力场的开发策略, 即兼顾高分子系统的结构性质以及热力学性质, 提出了一种系统化地开发聚合物的粗粒化力场的方法 力场优化过程中, 采用了自由能的 Lennard-Jones 势能函数形式 [2], 扩展了粗粒化力场的温度应用范围 作为研究示例, 我们详细讨论了聚二甲基硅氧烷和聚乙烯的粗粒化力场参数优化, 从分子的热力学和结构性质获得力场的温度依赖性质 对于高分子的多种性质, 如密度 表面张力 回旋半径 玻璃化转变温度 溶解度参数等, 我们验证了粗粒化力场模拟的结果, 得到了与全原子模拟和实验一致的结果 关键词 : 高分子 ; 聚合物 ; 粗粒化 ; 力场 ; 温度迁移参考文献 [5] Florian Müller-Plathe. Chem. Phys. Chem. 2002, 3:754. [6] Fenglei Cao, Huai Sun. J. Chem. Theory Comput. 205, : 4760. 30

P-4-06 A Density Functional Theory Study of Oxygen Vacancy Formation at the () Surface of γ-fe2o3 and (000) Surface of α-fe2o3 Author (Wei Jian), Corresponding Author(Fu-quan Bai),* (Zhang Hong-Xing) 2,* Institute of Theoretical Chemistry, University of Jilin, Liutiao Road, No 2, Changchun, P.R.China, 30023 *Email: jianwei6@mails.jlu.edu.cn, baifq@jlu.edu.cn, zhanghx@jlu.edu.cn Oxygen Vacancy Formation at the () Surface of γ-fe2o3 and (000) Surface of α-fe2o3 has been investigated using density functional theory. In agreement with experimental data, the reduced () surface of γ-fe2o3 which shows an occupied defect state -2.38 ev below the (000) surface of α-fe2o3 which shows an occupied defect state -.302 ev. For both the reduced surfaces, the excess charge associated with the defect states is primarily localized on two Fe sites neighboring the vacancy. Vacancy formation energies vary as ΔEγ <ΔEα,which shows that the oxygen on the surface of γ-fe2o3 is more easily separated from its surface than α-fe2o3. In order to maintain the activity of the catalyst, we considered the introduction of oxygen molecules to supplement the vacancy oxygen deficiency after the formation of vacancy oxygen. Compared to the surface energy of α-fe2o3, the surface energy of γ-fe2o3 is 3.59eV lower, indicating that γ-fe2o3 vacancies are also more likely to add oxygen molecules. We also found that the surface of the γ-fe2o3 surface in the oxygen molecules, the lattice of a surface oxygen molecules have a tendency to leave the surface. The calculated results indicate that the structure of aerobic departure trend is 3.449eV lower than the structural energy of oxygen in the original position. In other words, the oxygen in the γ-fe2o3 surface lattice is lively and easy to lose. It may be explained that this is a good reason for the catalytic activity of γ-fe2o3. Fig. Oxygen molecules are introduced to supplement oxygen vacancy: a) Side view of α-fe2o3 ; b) Top view of α-fe2o3; c) Side view of γ-fe2o3 ; d) Top view of γ-fe2o3; Fig.2 The yellow represents the oxygen of the position in the γ-fe 2O 3 :a) Top view and b) side view of γ-fe 2O 3 before the oxygen molecule was introduced; c) Top view and d) side view of γ-fe 2O 3 Keywords: oxygen vacancy; γ-fe2o3; α-fe2o3 References: [] Benjamin J. Morgan; Graeme W. Watson. J. Phys. Chem. C 2009, 3, 7322 7328. 302

P-4-07 Mechanistic Study in Functionalization of Quinolines: Patterns of Radical Regioselective C-H Activation Jingxing Jiang, Yan Liu 2, Zhuofeng Ke,* School of Materials Science and Engineering, Sun Yat-sen University, Guangzhou 50275 2 Shchool of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 50006 *Email: kezhf3@mail.sysu.edu.cn Radical transformations are useful tools for the synthesis and modification of heterocycles. It is important to understand the radical mechanism and the role of neutral radical, anion radical and cation radical in these kinds of transformations. We presents theoretical study for three representative systems of radical C-H functionalizations of quinolines (Copper-catalyzed sulfonation, Iodine-mediated amidation and Cobalt-catalyzed nitration) to illustrate the role of different type of radical species and the origin of the selectivity. The interesting mechanistic variations in these three radical transformations is oxidative/reductive abilities of metal/reagent center and the patterns of single electron transfer. The Cu(I) center prefers offering an electron to generate a Ts radical whereas Cu(II) cannot accept single electron from neutral radical. The Cu(II)-anion radicals undergo intermolecular SET to produce a new Ts radical instead of intramolecular SET to Cu(I) species. SET between I(III) reagent and heterocycle is not favored but the iodine reagent undergoes I-N cleavage to generate N(SO2Ph)2 radical which leads to neutral radical pathway subsequently. With respect to cobalt system, this reaction undergoes Co(II) cation radical mechanism after the oxidation by t-buo radical. The Co(II) functionalized species is oxidized by t-buo radical again to produce a new Co(II) cation radical. The preferential radical mechanism for the copper-catalyzed sulfonation and the iodine-mediated amidation are both favor C5-site functionalization. In cation radical mechanism for cobalt system, higher spin densities on the C5- and C7-site lead more stable coupled product (the majority of C5-product has its origins in a steadier coupled species). Fig. Radical Species in Regioselective C-H Functionalization of Quinolines: Which One is Favored? Keywords: Single Electron Transfer (SET), neutral radical, cation radical, anion radical, Density Functional Theory (DFT) References: [] J. Wei, J. Jiang, X. Xiao, D. Lin, Y. Deng, Z. Ke, H. Jiang and W. Zeng, J. Org. Chem., 206, 8, 946-955. [2] D. Ji, X. He, Y. Xu, Z. Xu, Y. Bian, W. Liu, Q. Zhu and Y. Xu, Org. Lett., 206, 8, 4478-448. [3] C. J. Whiteoak, O. Planas, A. Company and X. Ribas, Adv. Synth. Catal., 206, 358, 679-688. 303

P-4-08 Calculation of the Potential of Mean Force of a High-level Hamiltonian from a Low-level One: A Combination of the Weighted Histogram Analysis Method and Thermodynamic Perturbation Pengfei Li, Xiangyu Jia 2 3, Ye Mei 2,* State Key Laboratory of Precision Spectroscopy, School of Physics and Materials Science, East China Normal University, Shanghai 200062, China 2 NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China 3 Current address: NYU-ECNU Center for Computational Chemistry at NYU Shanghai, Shanghai 200062, China *Email: ymei@phy.ecnu.edu.cn The potential of mean force (PMF) is known as a useful tool in the study of chemical reactions. The calculations of PMF can be used to elucidate the reaction mechanism and predict the rates of chemical processes. In study of chemical reactions in condensed phase, quantum mechanics (QM) method is necessary to describe the electronic changes in chemical processes. As an efficient compromise between accuracy and efficiency, hybrid quantum mechanics/molecular mechanics (QM/MM) methods are very popular to simulate such chemical processes. As an extension of our previous work[], it is expected that (M)BAR[2]+TP[3] can be applied to calculate the PMF of chemical reaction. In this work, we give a rigorous method by combing WHAM[4] (or MBAR) and TP methods to calculate the PMFs of three different kinds of chemical reactions, including (a) SN 2 reaction of CH3Cl + Cl - Cl - + CH3Cl. (b) Glycine intramolecular proton transfer reaction from neutral form to zwitterion form. (c) Aliphatic Claisen rearrangement reaction of allyl vinyl ether (AVE) to 4-pentenal. We show that the PMF of high-level Hamiltonian can be obtained well from a low-level one by using MBAR+TP method, which avoids expensive sampling under high-level Hamiltonian. Keywords: potential of mean force; weighted histogram analysis method; thermodynamic perturbation; reference potential scheme; multiple Bennett s acceptance ratio; quantum mechanics/molecular mechanics References: [] Jia, X.; Wang, M.; Shao, Y.; König, G.; Brooks, B. R.; Zhang, J. Z. H.; Mei, Y. J. Chem. Theory Comput. 206, 2: 499. [2] Shirts, M. R.; Chodera, J. D. J. Chem. Phys. 2008, 29: 2405. [3] Zwanzig, R. W. J. Chem. Phys. 954, 22: 420. [4] Souaille, M.; Roux, B. Comput. Phys. Commun. 200, 35: 40. 304

P-4-09 General Hydrogen Activation Modes for Novel Lewis Acid Transition Metal (LA-TM) Catalysts Yinwu Li, Cheng Hou, Zhuofeng Ke* School of Materials Science & Engineering, Sun Yat-sen University, Guangzhou 50275 *Email: kezhf3@mail.sysu.edu.cn Hydrogen energy, as a cleanly renewable source, has great potential to meet global energy and environmental requirements. Therefore, many researchers devote themselves to seek efficient catalysts for renewable utilization of hydrogen energy via chemical bonds in mid conditions. At present, the popular method is to biomimic the function of active center in hydrogenase to activate H2 by Lewis base transition metal (LB-TM) catalysts, in which the Lewis base site abstracts proton and the transition metal center accepts hydride during heterolytic H2 cleavage. Our group present general hydrogen activation modes for novel type of Lewis acid transition metal (LA-TM) catalysts. Differ from traditional LB-TM catalysts, the LA-TM catalyst is conventionally new bearing an electron deficiency Lewis acid site for H2 activation, in which the Lewis acid site functions as electrophile to accept hydride during H2 cleavage. Using ( Ph DPB Ph )-Ni as a representative LA-TM catalyst, we presented four general hydrogen activation modes for the LA-TM catalyzed H2 activation vi systematically DFT studies, including: () the cis homolytic mode through a cis dihydride intermediate, in which Lewis acid stabilizes the dz 2 electron of transition metal; (2) the trans homolytic mode to a trans dihydride complex, in which the LA datively interacts with transition metal during cleavage; (3) the synergetic heterolytic mode, in which H2 cleaves cooperatively assisted by both the Lewis acid and transition metal; (4) the dissociative heterolytic mode, in which the Lewis acid and transition metal assist H2 cleavage in dissociative manner. These modes should provide a general mechanistic framework for the development and rational design of LA-TM catalysts in the future. Fig. General H2 activation modes for LA-TM catalysts. Keywords: Lewis acid transition metal; H2 activation; Mechanism; Homolytic; Heterolytic References: [] Harman, W. H.; Peters, J. C. J. Am. Chem. Soc. 202, 34, 5080. [2] Zeng, G.; Sakaki, S. Inorg. Chem. 203, 52, 2844. [3] Li, Y. W.; Hou, C.; Jiang, J. X.; Zhang, Z. H.; Zhao, C. Y.; Page, A. J.; Ke, Z. F. Acs Catal 206, 6, 655. 305

P-4-020 Theoretical Investigation on Diaurate-Catalysis Through C(sp 3 )-H Activation Zhi-Feng Li, Hui-Xue Li, Xiao-Ping Yang College of Chemical Engineering and Technology, Key Laboratory for New Molecule Design and Function of Gansu Universities, Tianshui Normal University, Tianshui 7400, P. R. China Email: zflitsnu@63.com Abstract: A wide range of gold-catalyzed reactions based on a dual activation mechanism has recently been reported in the literature. The diaurate-catalyzed synthesis of benzofulvenes through C(sp 3 )-H activation have been theoretically investigated with density functional theory (DFT). A comprehensive mechanistic DFT study of these reactions was carried out to better understand the experimental outcomes, and divergent and substrate-dependent mechanisms for the formations of benzofulvenes were uncovered based on the computational results. Free energy diagrams for three types of mechanisms were computed, one that leads to precatalyze through the dual-catalysis, another where the dual-catalysis path includes 8,9-H transferring, and one with a 8,9-H transferring through the single-catalysis path. The catalysis and the model catalysis have been used to investigated the mechanism. The calculated results which substantiates the dual activation mechanism previously published in literature rather than the proposed single activation in theory. In the pathway, the initial activation of the diyne has been shown to proceed via an intermolecular transfer of a cationic gold catalyst from the thermodynamically preferred geminal-, -acetylide complex to the active non-geminal analogue. Furthermore, the regioselectivity of a 5-endo-dig versus a 6-endo-dig cyclization has been addressed, and the 5-endo-dig cyclization in pathway was found to be most favorable both thermodynamically and with regard to the activation barrier. Additionally, the effect of the substitution is investigated and the reaction activity of title system is much substrate-dependent. Keywords: C(sp 3 )-H Activation, DFT, Benzofulvenes References: [] Hashmi, A. S. K.; Wieteck, M.; Braun, I.; Rudolph, M.; Rominger, F. Angew. Chem., Int. Ed., 202, 5: 0833. [2] Tokimizu, Y.; Wieteck, M.; Rudolph, M.; Oishi, S.; Fujii, N.; Hashmi, A. S. K.; Ohno, H. Org. Lett., 205, 7: 604. [3] Bucher, J.; Stößer, T.; Rudolph, M.; Rominger, F.; Hashmi, A. S. K. Angew. Chem., Int. Ed., 205, 54: 666 Acknowledgments: This work was supported by the National Natural Science Foundation of China (Grant No. 2463023, 246502, 2373277) 306

P-4-02 钯催化碘代芳烃, 苯甲酸酐和丙烯酸酯交叉偶联合成烯基化芳香酮的反应机理研究 梁玉洁 蒋原野 刘玉霞 毕思玮 * 曲阜师范大学化学与化工学院, 山东省曲阜市静轩西路 57 号, 27365, siweibi@26.com [] [2] 摘要芳香酮类化合物作为重要的产品和合成中间体, 广泛应用于药物化学, 材料科学以及天然产 [3] 物合成等各个领域 在以往的一些芳香酮类化合物的合成方法常出现区域选择性差 官能团兼容性低以及实验条件要求苛刻等问题 针对这些问题, 近来梁永民和许鹏飞课题组报道了一个 Catellani-Lautens 型的催化方法, 可将芳基碘, 酸酐和丙烯酸酯以优异的区域和立体选择性转化为烯 [4] 基化的芳基酮 我们利用密度泛函理论研究了该反应的详细反应机理, 澄清了反应的速率 / 区域选择性 / 立体选择性决定步以及影响因素, 揭示了降冰片烯在该类反应中除脚手架之外的作用, 以及需要使用当量降冰片烯的原因 关键词芳香酮 ; 区域选择性 ; 机理 ;DFT;Catellani-Lautens 参考文献 Luque-Ortega, J. R.; Reuther, P.; Rivas, L.; Dardonville, C. J. Med. Chem. 200, 53, 788-798. Sharmoukh, W.; Ko, K. C.; Noh, C.; Lee, J. Y.; Son, S. U. J. Org. Chem. 200, 75, 6708-67. Hatano, B.; Kadokawa, J. I.; Tagaya, H. Tetrahedron Lett. 2002, 43, 5859-586. Zhou, P.; Ye, Y.; Liu, C.; Zhao, L.; Hou, J.; Chen, D.; Tang, Q.; Wang, A.; Zhang, J.; Huang, Q.; Xu, P.; Liang, Y.; ACS Catal. 205, 5, 4927-493. 307

P-4-022 炸药晶体与溶剂界面相互作用的分子模拟研究刘英哲 *, 来蔚鹏, 尉涛, 马义丁 西安近代化学研究所, 陕西西安,70065 *Email: liuyz_204@63.com 炸药晶体形貌对炸药的感度等性能有重要影响, 了解炸药晶体的生长机制并预测不同条件下炸药的晶形对炸药晶体堆积密度的提升和安全性能的改善具有重要意义 本文通过理论方法模拟了炸药 RDX 在丙酮溶剂中结晶时五个主要晶面的结构 能量和动力学性质, 从分子水平上了解 RDX 在丙酮中结晶时的生长形貌 模拟结果表明, 溶剂的行为, 如质量密度分布 偶极矩取向 相互作用和表面扩散等, 依赖于 RDX 每个晶体表面的结构特点 基于占位分析 ( 见图 ), 可清晰地显示溶剂与炸药晶体的结合位点 从模拟轨迹中提取了典型的结合模式, 通过 M06-2X/6-3++G** 理论水平计算的各晶面结合能力排序依次为 (002) (20) > (200) > (020) > () 每个生长晶面的形态学重要性预测与实验数据较为吻合 (a) () (b) (200) (c) (020) (d) (002) (e) (20) Fig. Snapshots (top views) for binding sites of acetone molecules at the different crystal surfaces. The polar (N, O atoms) and nonpolar (C, H atoms) parts of RDX crystal surfaces exposed to solvent environment are distinguished in pink and white colors, respectively. The cyan isosurface corresponds to the AC occupancy of 0.8. 关键词 : 分子模拟 ; 吸附位点 ; 晶体形貌 参考文献 [] Liu, Y. Z.; Lai, W. P.; Ma Y. D.; Yu, T.; Kang, Y.; Ge, Z. X. J. Phys. Chem. B. 207, 2: 740. [2] Liu, Y. Z.; Yu, T.; Lai, W. P.; Ma Y. D.; Kang, Y.; Ge, Z. X. J. Mol. Graphics Modell. 207, 74: 38. [3] Liu, Y. Z.; Lai, W. P.; Yu, T.; Ma Y. D.; Kang, Y.; Ge, Z. X. RSC Adv. 207, 7: 305. 308

P-4-023 Theoretical Investigation of Ferroelectric Switching of Supramolecular Rotators Lingheng Luo, 2 and Shuang Chen,* School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu 20023, China 2 Kuang Yaming Honors School, Nanjing University, Nanjing, Jiangsu 20023, China *Email: chenshuang@nju.edu.cn Supramolecular Rotators undergo several possible mechanisms which change their dipoles to induce ferroelectric switching. Combined the density functional theory (DFT) calculations at the level of M06-2X/6-3G(d) with the Landau-Devonshire theory, the variation of energy of a supramolecular rotator with pendulum-like motion of its cation can be estimated to present the most possible rotational mechanism of this kind of ferroelectrics, agreeing with the experimental prediction, and in addition, the estimation of the Curie point and coercive field of this ferroelectric switching is ongoing. Fig. The variation of energy of a supramolecular rotator with pendulum-like motion of its cation. Keywords: Ferroelectric switching; supramolecular; rotator-stator; DFT calculations 309

P-4-024 光敏化能量转移驱动的立体选择性环加成反应的机理研究 马丽爽, 陈雪波,* 北京师范大学化学学院, 理论与计算光化学教育部重点实验室, 北京市新街口外大街 9 号,00875 *Email: xuebochen@bnu.edu.cn 有效实现不对称光环加成反应的关键是寻找有效控制立体选择性和抑制背景反应 避免外消旋产物的有效途径 引入金属复合物光催化剂, 以光敏化的方式驱动不对称环加成反应进行是实现绿色光化学合成的重要手段 这些复杂的反应涉及手性 Lewis 酸催化剂诱导的激发态能量调控和光催化剂主导的敏化传能等复杂过程, 科学界对其理解尚处在起步阶段, 有众多的理论问题亟待解决 我们采用多组态微扰理论并结合我们发展的 Dexter 能量转移数值计算方法, 对金属复合物光催化剂和手性 Lewis 酸催化调控的 [2+2] 光环加成反应进行了理论研究 ( 如 Fig 所示 ) 计算表明, 孤立的查尔酮底物吸收紫外光到达 ππ* 态, 系间窜跃到 3 ππ* 态, 得到双自由基中间体, 结合另一双烯底物生成一对外消旋 [2+2] 环加成对映异构体 但由于 ππ* 3 ππ* 之间的自旋轨道相互作用比较弱, 其系间窜越速率极低, 且在 ππ* 态存在快速的激发态质子迁移竞争弛豫路径, 因此背景反应效率并不高 当底物与 Lewis 酸催化剂配位时, 加成反应的三态能量显著降低, 使可见光敏化剂 Ru(bpy)3(PF6)2 提供的三态能量足以通过能量转移的方式活化底物, 得到三态双自由基中间体, 最终高效完成环加成反应 应用我们发展的 Dexter 能量转移数值模拟方案, 并结合计算得到的敏化传能理论模型, 估算出光催化剂发生有效传能的浓度范围, 为设计高效的光催化剂提供可靠的数据基础 我们的理论计算, 提出了 Lewis 酸配位的激发态能量调控和手性控制机制, 并揭示了能量转移在光催化循环体系中的有效实现形式, 为以理性预测为导向的光学活性手性分子的合成提供了理论基础和设计思路 关键词 : 多组态微扰理论 ; 光催化 ;[2+2] 环加成 ; 对映选择性 ; 能量转移 Fig. Regulatory mechanism of the enantioselective intermolecular [2+2] photocycloaddition reaction triggered by the Lewis acid catalyzed triplet energy transfer and asymmetric induction of chiral ligands 参考文献 [] Blum, T. R.; Miller, Z. D.; Bates, D. M.; Guzei, I. A.; Yoon, T. P. Science 206, 354: 39. [2] Miller, Z. D.; Lee, B. J.; Yoon, T. P. Angew. Chem. Int. Ed. 207, 56: 89. [3] Wang, H. J.; Cao, X. Y.; Chen, X. B.; Fang, W. H.; Dolg, M. Angew. Chem., Int. Ed. 205, 54: 4295. [4] Han, J.; Chen, X.B. J. Mater. Chem. C, 203, : 4227. 30

P-4-025 IMPROVING THE CORRELATION BETWEEN PREDICTED AND DETERMINED BIOACTIVITIES USING QUANTUM MECHANICS CHARGE Cheng Peng,2, J. Wang,*, Y. Yu,2, G. Wang,2, Z. Chen,2, Z. Xu, T. Cai, Q. Shao, J. Shi 3,*, W. Zhu,2,* Drug Discovery and Design Center, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai, 20203 2 University of Chinese Academy of Sciences, UCAS, No.9A Yuquan Road, Beijing, 00049 3 UCB Biopharma SPRL, Chemin du Foriest, Braine-l'Alleud, Belgium *Email: jawang@simm.ac.cn(jw); Jiye.Shi@ucb.com (JS); wlzhu@simm.ac.cn(wz) It is a great challenge to accurately predict the binding free energy (ΔG) of ligand to protein with limited computer resources. -3 However, the overall accuracy of such approach is unsatisfactory up to date. The approach using quantum mechanics/molecular mechanics (QM/MM) to calculate protein charges (QMPC) could significantly improve the accuracy of the ΔG calculation, which is however limited by its largely needed computer resource for QM/MM calculation. 4 To improve the accuracy and efficiency, we used 4 less computer resource consuming semi-empirical quantum mechanical (SQM) methods (AM, PM3, PM6 and PM7) to calculate QMPC, called SQMPC approach. With 50 ligands interacting with 5 different proteins as examples, we found that all SQMPC approaches produced very strong correlation with correlation coefficient R 2 greater than 0.6 between the predicted and experimentally determined bioactivity for all the examples, which is much better than the conventional approach. Especially, SQMPCAM (R 2 = 0.94) and SQMPCPM7 (R 2 = 0.98) have the best performance that is comparable to QMPCB3LYP (R 2 = 0.92) and is better than QMPCHF (R 2 = 0.83) in ER-ligand system. Among the semi-empirical methods, AM, PM7 and PM6 are better than PM3. In addition, the detailed analysis revealed that the electrostatic polarization introduced by SQMPC affects the electrostatic contribution to the binding affinity and thus, achieves better predictions. Interestingly, this work exemplified that longer MD simulation is not always necessary to accomplish better prediction of binding free energy. Thus, this comparative work provides an alternative approach to accurately and efficiently predicting ΔG of ligand to protein with potential of high throughput processing. Keywords: SQM; binding free energy calculation; electrostatic polarization; drug design References: [] Bakan, A.; Bahar, I. Proc. Natl. Acad. Sci. U.S.A 2009, 06: 4349 Chem. Phys. 20, 35: 4304. [2] Ferreira, L. G.; Dos Santos, R. N.; Oliva, G.; Andricopulo, A. D. Molecules 205, 20: 3384. [3] Steinbrecher, T. B.; Dahlgren, M.; Cappel, D.; Lin, T.; Wang, L.; Krilov, G.; Abel, R. J. Chem. Inf. Model. 205, 55: 24 [4] Wang, J.; Shao Q.; Cossins, B. P.; Shi, J.; Chen, K.; Zhu, W. J. Biomol. Struct. Dyn. 206, 34: 63 3

P-4-026 Tetra-silicene: A Semiconducting Allotrope of Silicene with Negative Poisson s Ratios Man Qiao, Yu Wang 2, Yafei Li,* Department of Chemistry, Nanjing Normal University, Nanjing city Qixia District Yuen Road No. building campus, the Nanjing Normal University Xianlin,Nanjing 20046 *Email: liyafei.abc@gmail.com By means of comprehensive density functional theory (DFT) computations, we designed a new two-dimensional (2D) structure of silicon, namely, tetra-silicene. In tetra-silicene, each silicon atom binds with four neighboring Si atoms to form a 2D network composed of only tetragons. Our DFT computations demonstrate that tetra-silicene is of rather high experimental feasibility, as indicated by its considerable cohesive energy, all positive modes in the phonon spectrum, and the well maintained structure after 0 ps first principles molecular dynamics simulations at 500 K. Tetrasilicene has rather intriguing mechanical properties featured with unusual negative Poisson s ratios. Remarkably, different from hexagonal silicene (hexa-silicene) which is semi-metallic without a band gap, tetra-silicene is semiconducting with an appreciable indirect band gap of 0.9 ev, and it has a considerable carrier mobility of 639.07 cm 2 V s. Encouragingly, our simulations suggest that tetra-silicene can be flexibly produced from hexa-silicene via mechanical conversion. Once synthesized, tetra-silicene would find many important applications in electronics and mechanical devices. Keywords: two-dimensional; tetra-silicene; hexa-silicene; carrier mobility; negative Poisson s ratios References: [] Qiao, M.;Wang, Y.; Li, Y.; Chen, Z. J. Phys. Chem. C. 207, 2: 9627 9633. 32

P-4-027 表面活性剂与油水界面的介观模拟研究 任强 *, 侯研博, 代振宇, 周涵 中国石油化工股份有限公司石油化工科学研究院, 北京, 00083 *Email: renqiang.ripp@sinopec.com 摘要 : 用介观模拟方法对两种类型的表面活性剂分子在油水界面的分布形态进行了模拟 发现与单链型表面活性剂相比, 低聚型表面活性剂分子由于其空间结构上的分散性导致与其通过化学键相连的部分极性基团进入油分子内部, 在油水界面处相对更靠近油相, 使得低聚型表面活性剂分子在油水界面处极性基团的排列没有单链型表面活性剂那样排列有序 ; 低聚型表面活性剂存在时, 油水界面的接触面积相对较大, 而表面活性剂在油水中的分布相对比较均匀 ; 低聚型表面活性剂分子可以更好地降低油水界面的表面张力 ; 与低聚型表面活性剂分子结合的油由于受到更大的作用力而更容易脱离原附着物, 从而提高原油采出率 关键词 : 表面活性剂 ; 油水界面 ; 介观模拟 参考文献 [] Laschewsky A, Wattebled L, Arotcarena M. Langmuir,2005, 2: 770. [2] Zhang, S.; Li, S.; Zhou, W.; Zheng, L. Chem. Phys. 20, 35: 4304. [3] Murguia M C, Grau R J. Syn Lett,200, 8: 229. [4] Groot R D.Langmuir,2000,6(9):7493. [5] Groot R D,Madden T J.J of Chem Phys[J].998,08(20):873. [6] Groot R D,Madden T J,Tidesley D J. J of Chem Phys,999,0(9):9739. [7] Zhang K,Charles W M.Comput Phys Commun,2000,29:275. [8] 任强, 代振宇, 周涵. 石油学报 ( 石油加工 ),203,29():86. [9] 任强, 代振宇, 周涵. 石油炼制与化工,203,44(4):39. 33

P-4-028 杂芳基二氢嘧啶类抑制剂与 HBV 的构效关系和作用机制研究 屠晶 李姣姣 单志杰 宋丽婷 翟红林* 兰州大学化学化工学院 兰州 730000 *Email: zhaihl@63.com 抗乙型肝炎病毒 HBV 药物因其副作用和耐药性病毒株的出现面临挑战 非核苷类药物由于其 较好的疗效和较低的副作用 已被开发用于抑制HBV 杂芳取代的二氢嘧啶 HAP 化合物是其中的 一类非核苷类药物 能够有效地抑制HBV衣壳的形成 在本文中 我们通过三维定量构效关系 分子 动力学模拟和结合自由能分解探索了HBV衣壳蛋白与HAP化合物的作用机制及Y32A突变对该类药物 抑制蛋白的影响 比较分子场 CoMFA 模型和比较分子相似性指数分析 CoMSIA 充分解释了HAPs 与HBV的构效关系 结合自由能分析与实验数据表明 HAP骨架和残基Trp02之间的氢键相互作用是 稳定HAPs与HBV结合构象的关键因素 非极性贡献是增强HAP抑制活性的主要驱动力 Y32A突变加 强了抑制剂2与HBV的结合亲和力 对HAPs-HBV的构效关系和作用机制的解析 可以为合理设计更有 潜力的HAP类型的HBV抑制剂提供分子水平上的依据 Fig. Comparison of per-residue energy decomposition for key residues for two systems. (a) Conformational comparison of the 2-HBV and 24-HBV (carbon atoms are colored in blue and green, respectively); (b) The comparison of the contributions of the van der Waals interaction for key residue to the binding of inhibitors 2 and 24. 关键词 二氢嘧啶 HAP HBV衣壳蛋白 定量构效关系 分子动力学 结合自由能计算 参考文献 [] Bourne, C.; Lee, S.; Venkataiah, B.; Lee, A.; Korba, B. Finn, M. G.; Zlotnick, A. J. Virol. 2008. 82: 0262. [2] Bourne, C. R.; Finn, M.; Zlotnick, A. J Virol 2006, 80: 055 [3] Zlotnick, A.; Ceres, P.; Singh, S.; Johnson, J. M. J Virol 2002, 76: 4848 [4] Klumpp, K., Lam, A. M., Lukacs, C., Vogel, R., Ren, S., Espiritu, C., Baydo, R., Atkins, K., Abendroth, J., Liao, G., Efimov, A., Hartman, G., Flores, O. A., Proc. Natl. Acad. Sci. U. S. A. 205,2: 596-520 [5] Wang, P.; Naduthambi, D.; Mosley, R.T.; Niu, C., Furman, P.A.; Otto, M.J.; Sofia, M.J. Bioorg. Med. Chem. Lett. 20, 2: 4642 34

P-4-029 阴离子 阴离子型卤键作用的理论研究 王桂敏,#, 陈照强,#, 徐志建,*, 王进安, 杨洋, 蔡婷婷, 施继烨 2,*, 朱维良,* 中国科学院受体结构与功能重点实验室, 中科院上海药物研究所, 药物发现与设计中心,20203; 2 UCB 生物制药公司, 比利时 *Email:zjxu@simm.ac.cn; Jiye.Shi@ucb.com; wlzhu@mail.shcnc.ac.cn. 卤键是卤素原子的 σ- 空穴 (σ-hole) 与亲核试剂之间形成的非共价相互作用 在生理条件下, 药物分子可能呈现出不同的质子化状态 含卤小分子去质子化后, 卤素头部正电性的 σ- 空穴会消失, 可能与同样带负电荷的亲核分子相互排斥 经过数据库搜寻, 我们发现带负电荷的分子之间存在具有卤键几何特征的作用模式 基于对卤苯甲酸和丙炔酸的复合物的量化计算表明阴离子 - 阴离子型卤键在真空中是不稳定的, 而在溶剂中可以稳定存在 卤键作用距离和能量均说明阴离子 - 阴离子型卤键较中性分子间的卤键更强, 自然键轨道 (NBO) 和分子中的原子的量化理论 (QTAIM) 的分析同样证实了上述结论 运用对称性匹配微扰理论 (SAPT) 进行能量分解后, 我们发现诱导作用对分子间的相互吸引贡献很大 我们从蛋白晶体数据库 (PDB) 中选取了 4 个蛋白 - 配体复合物, 利用量子力学 / 分子力学杂交方法进行了计算, 结果提示阴离子 - 阴离子型卤键可以提高配体的亲和力, 最大作用能接近 3kcal/mol 关键词 : 卤键 ; 阴离子 ; 量子力学 / 分子力学 ; 药物设计 参考文献 [] Wang, G.; Chen, Z.; Xu, Z.; Wang, J.; Yang, Y.; Cai, T.; Shi, J.; Zhu, W. J. Phys. Chem. B 206, 20 (4): 60. 35

P-4-030 Experimental and Theoretical Studies of the Reactions of Ground-State Sulfur Atoms with Hydrogen and Deuterium Han Wang, Yongle Li,* Department of Physics and International Center of Quantum and Molecular Structures, Shanghai University, Shanghai, 200444, China *Email: yongleli@shu.edu.cn The gas-phase kinetics of S( 3 PJ) atoms with H2 and D2 have been studied via the laser flash photolysis resonance fluorescence technique. S atoms were generated by pulsed photolysis of CS2 at 93 nm and monitored by time-resolved fluorescence at 8 nm. Here we employ a newly developed triplet PES using the high-level ab initio data reported in a recent publication to investigate the kinetics for formation of SH(SD) + H(D) using ring polymer molecular dynamics (RPMD) rate theory 2 and canonical variational transition-state theory. The RPMD approach enables the inclusion of quantum mechanical zero-point energy and tunneling which are expected to be significant for these heavy-light-light systems involving hydrogens. There is excellent agreement above about 000 K. At lower temperatures, the experimental rate coefficient is substantially larger than the results computed for the adiabatic reaction, suggesting a significant role for intersystem crossing to the singlet potential energy surface at lower temperatures. The comparison between the experimental data and the single-surface theoretical rate coefficients with the inclusion of tunneling will thus shed light on the importance of intersystem crossing in these reactions. Fig. Comparison of rate coefficients obtained by RPMD (Conv. denotes the converged number of beads, and bead denotes single bead is used), CVT/μOMT and experiments for the S+H2 reaction. Fig. 2 Comparison among RPMD (Conv. denotes the converged number of beads, and bead denotes single bead is used), CVT/μOMT and experimental rate coefficients for the S+D2 reaction. Keywords: one; molecular dynamics simulation; intersystem crossing; References: [] B. Kolb, P. Marshall, B. Zhao, B. Jiang and H. Guo, J. Phys. Chem. A 2, 2552-2557(207). [2] Y. V. Suleimanov, F. J. Aoiz and H. Guo, J. Phys. Chem. A 20, 8488-8502 (206). 36

P-4-03 聚合物拉伸应力松弛的蒙特卡罗分子模拟 王季平, 胡文兵 * 南京大学化学化工学院高分子系, 配位化学国家重点实验室, 南京,20023 *Email: wbhu@nju.edu.cn 聚合物拉伸流动加工例如纺丝 注塑 吹拉膜和发泡过程中不可避免地伴随着聚合物的应力松弛行为 此前我们开发的聚合物拉伸诱导结晶的蒙特卡罗模拟只考虑了拉伸应变过程, 对应于交联网络中橡胶分子链应变诱导结晶的情况 [-3] 我们在此基础上, 设法引入分子链构象应力松弛, 以加强理论模拟与真实聚合物流动取向加工过程的联系 本工作建立了一个合理的拉伸应力松弛模拟方法, 并展示了模拟所取得的一些初步结果 : 结合聚合物应力松弛典型的德拜松弛行为以及微观上粒子做布朗运动的特性, 将一个随高分子线团质量中心运动不断变化的力场引入到原有的抽样函数中 在高温下模拟所得到的应力特征松弛时间符合阿伦尼乌斯型温度依赖关系, 我们通过改变活化能的数值大小来反映不同聚合物的松弛快慢行为 采用这个模拟方法, 我们可以进一步研究应力松弛行为对拉伸诱导聚合物结晶行为的影响, 将有助于我们深入理解聚合物加工成型的微观结晶机理 致谢本工作得到国家自然科学基金委 (No. 227406, 2474050) 的资助! 关键词 : 蒙特卡洛模拟 ; 聚合物拉伸 ; 应力松弛 ; 参考文献 [] Nie, YJ.; Gao, HH.; Yu, MH.; Hu, ZM.; Reiter, G.; Hu, WB. Polymer. 203, 54: 3402-3407. [2] Nie, YJ.; Gao, HH.; Wu, YX.; Hu, WB. Soft Matter. 204, 0: 343-347. [3] Nie, YJ.; Gao, HH.; Hu, WB. Polymer. 204, 55: 267-272. 37

P-4-032 DFT study on the mechanism of carbon dioxide activation by transition metal complexes Author (Jing Wang), Corresponding Author(Jia Ran),* (Zhang Hong-Xing) 2,* Institute of Theoretical Chemistry, University of Jilin, Liutiao Road, No 2, Changchun, 30023 *Email: wangjing6@mails.jlu.edu.cn, jiaran@jlu.edu.cn, zhanghx@jlu.edu.cn Carbon dioxide (CO2) has been recognized as a greenhouse gas causing global warming. CO2 activation and conversion has attracted the great interest due to their scientific and industrial importance. Accordingly, further understanding of the CO2 activation is needed. A computational study with the B3LYP hybrid functional theory has been used to investigate the mechanism of the activation and cleavage of CO2 by the complexes Fe(C5H4)2P2EPh4 (E=Co, Ni, Cu) with coupling reactions. By comparing different transition metal complexes, our calculations show that Fe(C5H4)2P2EPh4 is capable of activating and cleaving CO2.The reactivity of the P2-Ni bond toward CO2 activation led to the strongest activation, while P2-Cu bond toward CO2 activation lead to the weakest activation. In addition, with the metallic species E becomes heavier, the activation barriers present a moderate rise. Because of the competitive nature between the different transition metals, the reactions and other factors significantly affect the reaction outcome, all of which have been discussed in detail. Fig. Proposed Oxidative Coupling Mechanism Keywords: CO2 activation; B3LYP; Transition metal complexes; Reaction barrier References: [] Alireza, A.; Nigel J. B.; Robert, S.; Organometallics.20,30:340-349. [2] Nguyen, N. H.; Le, V. K.; Le, M. C.; J Mol Model.205, 2:322. [3]Li J.; Jia G. C.; Lin Z. Y.; Organometallics.2008, 27:3892-3900. [4]Marius-Christian, S.; Aleix, C.V.; Christophe, C.; ACS Catal.206, 6:450-4505. 38

P-4-033 光诱导电子转移调控的 C-H 官能团化反应机理研究 王娟娟, 陈雪波,* 北京师范大学化学学院, 理论与计算光化学教育部重点实验室 北京市新街口外大街 9 号,00875 *Email: xuebochen@bnu.edu.cn 催化反应是当代合成化学的核心和基础, 以 Ir (III) 为代表的光催化剂能够有效吸收可见光, 产生的激发态中间体能够显著改变底物的反应特性, 获得多种通过传统的热化学反应难以实现的独特目标产物, 实现 绿色 合成 光催化反应涉及复杂的电子转移调控机制, 为了探索该机制, 我们拓展和运用多组态微扰理论, 并结合 Marcus 电子转移速数值计算方案, 建立了适用于酰胺导向的远端 C-H 官能团化反应机理研究的理论模型, 系统研究了其光催化循环机制 通过高精度激发态电子结构计算, 研究催化剂的激发态性质, 得到光催化剂电子跃迁与可见光吸收谱带的对应关系, 揭示其谱带展宽和吸收增强的根本原因 通过激发能计算, 建立可见光催化剂的吸收 / 发射光谱与配位结构及配体取代之间的定量构效关系 通过最低能量反应势能面计算, 揭示质子耦合的电子转移调控光催化反应的具体过程, 并结合电子转移速率计算, 评估光催化剂的催化效率 计算表明,Ir (III) 光催化剂在吸收可见光后, 快速弛豫到 3 dπ * 态极小, 诱导从酰胺底物到催化剂的单电子转移反应, 形成 3 nπ* 态, 初步活化 N-H 键 ; 在碱的作用下, 依赖六元环过渡态结构, 发生协同的,5- 氢迁移和碱的质子抽取反应, 生成相应的自由基中间体, 随后与烯烃发生 C-C 耦合作用, 实现远端 C(sp3)-H 键的官能团化 最后, 再次通过酰胺 碱和底物的质子耦合电子转移作用, 催化剂复原, 质子回迁 我们提出的协同机制为理解基于未官能团化的简单酰胺引导 C-C 键合成反应提供了重要的理论基础 关键词多组态微扰理论 ; 光催化 ; 电子转移 ;C-H 活化 ; 电子转移 参考文献 []Choi, G. C.; Zhu,Q.L.; Miller, D. C.; Gu, C. J.; Knowles, R. R. Nature 206,539, 268. [2]Chu, J. K.;R, T. Nature 206, 539, 275 [3]Shaw, M. H.; Twilton, J.; MacMillan, D. W. C. J. Org. Chem. 206, 8, 6898. [4]Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 203, 3, 5322. [5]Wang, H. J.; Cao, X. Y.; Chen, X. B.; Fang, W. H.; Dolg, M. Angew. Chem. Int. Ed. 205, 54: 4295. [6]Wang, H. J.; Fang, W. H.; Chen, X. B.; J. Org. Chem. 206, 8: 7093. 39

P-4-034 Quasi-Planar Pentacoordinate Silicon in CaSi Monolayer Yu Wang, Yafei Li * College of Chemistry and Materials Science, Jiangsu Key Laboratory of Biofunctional Materials, Nanjing Normal University, Nanjing 20023, Jiangsu, China. *Email: liyafei@njnu.edu.cn Chemical bonding is one of the most important concepts in chemistry. Basically, the properties of materials are defined by the type of atoms they contain and how they are bonded together. In this work, we computationally extend the rule-breaking chemical bonding of planar pentacoordinate silicon (ppsi) into the periodic system: a C2v Ca4Si22 molecular building block containing a ppsi center is identified firstly, followed by the construction of two-dimensional (2D) CaSi monolayer. Our computations demonstrate that the ppsi-containing CaSi monolayer has good thermodynamic, kinetic, and mechanical stabilities and is the global minimum structure in 2D space. CaSi monolayer is semiconducting with a moderate band gap of 0.5 ev and exhibits an unusual negative Poisson s ratio. These exceptional properties make CaSi monolayer a promising candidate for electronics and mechanics. Keywords: CaSi monolayer; planar pentacoordinate silicon; two-dimensional semiconductor; negative Poisson s ratio 320

P-4-035 嵌段共聚物溶剂蒸发退火成胶束的分子动力学模拟 王钰璋, 周嘉嘉,* 北京航空航天大学化学学院, 北京市海淀区学院路 37 号,009 *Email: jjzhou@buaa.edu.cn 利用耗散粒子动力学方法研究了均匀分散有两嵌段共聚物的良溶剂液滴在不良溶剂环境中发生溶剂蒸发退火的行为 通过改变嵌段共聚物的两部分与两种不同溶剂的排斥作用参数, 研究了不同情况下产生的聚合物胶束的不同形态 我们发现胶束的形态主要以两种方式呈现, 即椭球型的平行层状胶束和球型的洋葱状胶束 除此之外还有种类丰富的过渡形态 关键词 : 嵌段共聚物 ; 胶束 ; 分子动力学 参考文献 Fig. Solvent vapor annealing [] Anatoly V. Berezkin; Christine M. Papadakis; Igor I. Potemkin; Macromolecules 206, 49, 45 424 [2] Jae Man Shin; YongJoo Kim; Hongseok Yun; Gi-Ra Yi; Bumjoon J. Kim; ACS Nano; 207, (2), 233 242 32

P-4-036 The charge transfer at the interface of dye@g/at(0) Author (Jian-Ying Xi), Corresponding Author(Jia Ran),* (Zhang Hong-Xing),* Institute of Theoretical Chemistry, Jilin University, Liutiao Road No. 2, Changchun, P.R.China, 30023 *Email: jiaran@jlu.edu.cn, zhanghx@jlu.edu.cn Abstract: The main goal of this work is to study the charge transfer at the interface of graphene enhanced dye sensitized TiO2 solar cell system by using first-principles calculations based on density functional theory (DFT). The three promising anchoring groups (i.e., carboxylate, hydroxamate and phosphate) are adsorbed onto the graphene, TiO2 anatase (0) surface, and graphene/anatase(0) surface (G/AT(0)), respectively, which build the three proposed models: dye@g, dye@at(0) and dye@g/at(0). The quantum dynamics descriptions of the interfacial electron transfer (IET) are presented. By comparing the injection times, we believe that the implications of these findings could be relevant for building more efficient dye-sensitized solar cell (DSSC) through enhancing the charge carrier separation and transfer. Fig. The sketches for the adsorptions of the hydroxamate, carboxylate and phosphate on monolayer graphene. Fig.2 The interfacial electron transfer between catechol and the (0) surface of TiO 2 anatase. Keywords: Graphene; TiO2 Anatase; Interface; Electron Transfer References: [] Li, W.; Rego, L. G. C.; Bai, F. Q.; J. Phys. Chem. Lett. 204, 5: 3992-3999. [2] Li, X. H.; Gao, H. T.; Liu, G. J.; Comput. Theor. Chem. 203, 025: 30-34. [3] Geng, W.; Liu, H.; Yao, X.; Phys. Chem. Chem. Phys. 203, 5(6): 6025-6033. 322

P-4-037 全氟代烷烃全原子力场开发 向衍, 孙淮,* 上海交通大学化学化工学院, 上海市闵行区东川路 800 号上海交通大学,200240 *Email: huaisun@sjtu.edu.cn TEAM 力场 [] 中关于氟代烷烃的参数是没有温度迁移性的 我们在其基础上开发了一套关于全氟代烷烃的全原子力场参数 以 至 5 个碳的直链全氟代烷烃的密度, 蒸发焓的实验数据作为目标性质来得到分子间相互作用的力场参数 力场具有很好的温度迁移性, 各个分子从熔点到沸点都能跟实验数据较好的符合 结果如下 : Fig. 全氟代烷烃在不同温度下的密度与蒸发焓 关键词 : 分子模拟 ; 力场 ; 全氟代烷烃 ; 温度迁移性 参考文献 [] Jin, Z.; Yang, C.; Cao, F.; Li, F.; Jing, Z.; Chen, L.; Shen, Z.; Xin, L.; Tong, S.; Sun, H. J. Comput. Chem. 206, 37 (7), 653 664. 323

P-4-038 高分子冷结晶行为的蒙特卡罗分子模拟 * 徐承欢, 王季平, 胡文兵 南京大学化学化工学院高分子系, 配位化学国家重点实验室, 南京,20023 *Email: wbhu@nju.edu.cn 为了研究在低温区冷结晶过程中高分子的结晶行为, 我们在原有的格子链动态蒙特卡罗分子模拟的基础上 [], 修改了与高分子链构象相关的能量参数 Ec, 并引入了与温度相关的的参数 Ef, 用于表示高分子链段之间的黏结作用 通过逐一改变各个能量参数, 对高分子本体体系进行一系列升降温过程的模拟, 结果符合实际高分子在升降温过程结晶行为的基本特点 我们进一步分析此过程中结晶度随温度的变化情况和高分子链的形态, 从而得出各个能量参数对高分子结晶行为的影响 本工作对于研究高分子在低温条件下的冷结晶现象具有重要意义 关键词 : 分子模拟 ; 蒙特卡罗 ; 结晶 致谢 : 本工作得到国家自然科学基金委 (No.2474050) 的资助! 参考文献 [] Hu, W.-B.; Frenkel, D. Polymer crystallization driven by anisotropic interactions. Advances in Polymer Science 2005, 9, -35. 324

P-4-039 基于 LPL 的泽泻醇调脂分子机制研究 徐飞,*, 陆彩, 吴启南, 于慧 2, 陈军, 谷巍 南京中医药大学药学院, 南京,20046 2 江苏省中医院血液科, 南京,20029 *Email: 662386@ qq.com 摘要 : 目的 : 基于脂蛋白脂酶 (LPL) 进行泽泻的调血脂机制的研究 方法 : 建立高脂血症小鼠模型, 利用试剂盒法测定泽泻调脂有效成分泽泻醇单体 混合物及有效部位的调血脂作用及对调节甘油三酯 (TG) 关键酶 LPL 活性的影响, 通过同源建模得 LPL 分子结构, 利用分子模拟技术对泽泻醇单体及 : 混合物与 LPL 的相互作用机制进行研究 结果 : 泽泻醇单体 混合物 有效部位均可降低 TG 总胆固醇 (TC) 水平, 升高高密度脂蛋白 (HDL-C) 水平, 作用强度 : 混合物 > 单体 > 有效部位 泽泻醇单体 混合物及有效部位均可增强 LPL 活性, 增强程度 : 有效部位 > 混合物 > 单体 分子模拟研究表明,23- 乙酰泽泻醇 B 作用于 LPL N 端, 24- 乙酰泽泻醇 A 作用于 LPL C 端, 且与 Cys306 形成氢键, 二者 : 组合与 LPL 结合更强, 二者均作用于 N 端, 24- 乙酰泽泻醇 A 与 Arg8 形成氢键 结论 : 泽泻醇单体 混合物及有效部位均可调血脂 增强 LPL 活性, 说明泽泻醇可能是通过增强 LPL 的活性来降低 TG 水平, 同时 23- 乙酰泽泻醇 B 和 24- 乙酰泽泻醇 A 对 LPL 存在协同作用, 并且泽泻中除了这两者之外的泽泻醇对 LPL 也存在协同作用 LPL 的 N 端及 C 端均为其调脂催化活性区,Cys306 为其调脂关键氨基酸残基 ;C 端间接参与酶解过程, 二者 : 组合与 LPL 结合更强, 均作用于 N 端,24- 乙酰泽泻醇 A 与 Arg8 形成氢键 泽泻醇侧链与母环折叠则与 LPL 结合强, 侧链打开则与 LPL 结合弱, 说明泽泻醇侧链可能是其与 LPL 作用的关键基团 该结果为泽泻的临床应用 泽泻醇类系列结构的分子设计和作用机制研究提供有益的参考 Fig. Overall pattern of the interaction between alisol acetates and LPL ( alisol B 23-acetate is denoted by a ball and stick chart, alisol A 24-acetate is denoted by a stick chart) 关键词 : 混合物 ;LPL; 试剂盒法 ; 分子模拟 参考文献 [] Hassan, M; Abbas, Q; Ashraf, Z; Moustafa, AA. Comput Biol Chem. 207, 68: 3. [2] Kundu, P; Chattopadhyay, N. J Photochem Photobio B. 207,73:485. [3] Bagherzadeh, K; Shirgahi Talari, F; Sharifi, A; Ganjali, MR. J Biomol Struct Dyn. 205, 33(3): 487. 325

P-4-040 Supramolecular Catalysis in the Methylation of meta-phenylene Ethynylene Foldamer Containing N, N-Dimethylaminopyridine Lina Xu* College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035 *Email: xulina@wzu.edu.cn Density functional theory calculations were performed to elucidate the mechanism of the methylation reaction of N, N-dimethylaminopyridine (DMAP)-modified meta-phenylene ethynylene foldamer with eight methyl sulfonate esters with different alkyl groups. The helical structure of the DMAP-modified mpe foldamer results from multiple intramolecular π-π stacking interactions between m-phenylene ethynylene arms, which can be characterized by the helical energy. The noncovalent interactions between the foldamer and the substrate can stabilize the transition state and result in an acceleration of the methylation reaction of the foldamer. Due to the different shapes of the alkyl chains of the methylating agents, the methylation rates of the foldamers with linear and branched substrates show different rules. It is expected that these mechanistic insights into supramolecular catalysis can be used in the design and preparation of supramolecular catalysts and reactors. Fig. Supramolecular Catalysis in the Methylation of meta-phenylene Ethynylene Foldamer Containing N, N-Dimethylaminopyridine Keywords: Supramolecular Catalysis; Foldamer References [] J. Kang and J. Rebek Jr., Nature, 997, 385, 50-52. [2] T. Iwasawa, R. J. Hooley and J. Rebek Jr., Science, 2007, 37, 493-496. [3] M. Yoshizawa, M. Tamura and M. Fujita, Science, 2006, 32, 25-254. [4] D. M. Kaphan, M. D. Levin, R. G. Bergman, K. N. F. Raymond and D. Toste, Science, 205, 350, 235-238. [5] L. Xu, W. Hua, S. Hua, J. Li and S. Li, J. Org. Chem., 203, 78, 3577-3582. [6] L. Xu, S. Hua and S. Li, Chem. Commun., 203, 49, 542-544. [7] L. Xu, G. Fang, Y. Cao and A. Li, Phys. Chem. Chem. Phys. 206, 8, 3223-3229. [8] L. Xu, G. Fang and S. Li, RSC Adv., 207, 7, 4046-4052. 326

P-4-04 Probing Electric Field Effect on the catalytic performance of Mn-doped Graphene to CO oxidation Xian-Yan Xu,,* Huishi Guo, Cunyuan Zhao 2 College of Chemistry and Environmental Engineering, Shaoguan University, Shaoguan 52005, China. 2 MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 50275, China. *Email: sofiaxxy@hotmail.com Electric field is an effective route to tune the performance of catalysts. Here, we have probed the change of CO/O2 adsorption, the reaction mechanism of CO oxidation on Mn-doped graphene as a result of the externally applied electric field and provided a theoretical understanding of the rule by density functional theory (DFT) calculation. On the basis of DFT calculations, we suggest that increasing the negative direction electric field can strengthen the adsorption ability of CO/O2 onto Mn-Gr, leading to the easier dissociation of O-O bond and accelerate the CO2 formation. But it also results in the stronger binding between CO2 and the catalyst, and thus hinder CO 2 desorption. Therefore, considering the CO 2 formation and desorption, 0.50 F/Å in the negative electric field direction are recommended for CO oxidation on Mn-Gr with an reaction barrier of 0.55 ev. Keywords: electric field; CO oxidation; Mn-doped graphene; density functional theory References: [] Zhang, T.; Xue, Q.; Shan, M.; Jiao, Z.; Zhou, X.; Ling, C.; Yan, Z. J. Phys. Chem. C 202, 6(37): 998-9924. [2] Song, E. H.; Yan, J. M.; Lian, J. S.; Jiang, Q. J. Phys. Chem. C 202, 6 (38): 20342-20348. [3] Jiang, Q. G.; Ao, Z. M.; Li, S.; Wen, Z. RSC Adv. 204, 4 (39): 20290-20296. [4] Xu, X.-Y.; Li, J.; Xu, H.; Xu, X.; Zhao, C. New J. Chem. 206, 40 (: 936-9369. 327

P-4-042 Theoretical Study of Organic Sensitizers for High Efficient D A π A Dye-Sensitized Solar Cells Yongxin Xu, Minjie Li *, Wencong Lu * Department of Chemistry, Shanghai University, Shangda Rd, Shanghai, 200444 *Email: minjieli@shu.edu.cn, wclu@shu.edu.cn Compared with the traditional silicon-based solar cells, the dye-sensitized solar cells (DSSCs) have the characteristics of high photoelectric conversion efficiency and low production cost, so it has a wide application prospect in today's research field []. However, the absorption band of most organic dye sensitizers is limited to the partially visible regions, which affects the photoelectric conversion efficiency of DSSCs. We have designed a series of D-A-π-A non-metallic organic dye molecules based on IQ [2] by adding auxiliary acceptor. [3] Density functional theory (DFT) and time dependent density functional theory (TD-DFT) were employed to study the photovoltaic properties of the dyes such as ultraviolet absorption wavelength, HOMO and LUMO distributions, density of state and electron injection (Fig. ). The results show that the introduction of auxiliary heterocyclic acceptor exhibits a very narrow band gap compared to IQ, which results in a significant red shift of the maximum absorption wavelength in the visible - near infrared region. The maximum absorption wavelength of the PISQ even reached 974 nm. Compared with IQ, some other key parameters related to J SC and V OC of PISQ such as the injection driving force, the regenerative driving force and the total conduction band of the semiconductor substrate have been significantly improved. Therefore, these new sensitizers will be promising candidates for improving DSSCs performance. Fig. Photoelectric properties of PISQ and other dyes Keywords: molecular design; dye sensitizer; auxiliary receptor; density functional References: [] Gratzel, M., Photoelectrochemical Cells. Nature 200, 44: 338. [2] Pei, K.; Wu, Y.; Wu, W.; Zhang, Q.; Chen, B.; Tian, H.; Zhu, W., Chemistry-a European Journal 202, 8 (26): 890-8200. [3] Li, M.; Kou, L.; Diao, L.; Zhang, Q.; Li, Z.; Wu, Q.; Lu, W.; Pan, D.; Wei, Z., The Journal of Physical Chemistry C 205, 9 (8): 9782-9790. 328

P-4-043 Novel carbon nanotubes from 6,6,2-Graphyne Author (Dong-Chun Yang), Corresponding Author(Jia Ran),* (Zhang Hong-Xing) 2,* Institute of Theoretical Chemistry, University of Jilin, Liutiao Road, No 2, Changchun, P.R.China, 30023 *Email: yangdc4@mails.jlu.edu.cn, jiaran@jlu.edu.cn, zhanghx@jlu.edu.cn Two kinds of novel carbon nanotubes, namely (N, 0) and (0, N) 6,6,2- graphyne nanotubes are constructed by rolling up the rectangular 6,6,2-graphyne sheets along two different sides into cylinders. The mechanic and electronic properties of 6,6,2-GNTs with varied N from 3 to 20 are investigated by using density functional theory. Unlike the single wall carbon nanotubes, the Young s moduli of 6,6,2-GNTs are not remained constant in case of (N, 0), but the (0, N) tubes possess almost the same one around 0.32 TPa. The band structures and density of states are also exhibited in this work. When the tube sizes N are bigger than four, Dirac points appear at Fermi level in the band maps of (N, 0) type 6,6,2-GNTs following an even-odd law, while the (0, N) tubes are narrow gap semiconductors with tiny band gaps between 5.5 and 247.3 mev. Fig. (a) The sketches for the6,6,2-graphyne and its first Brillouin zone. (b) Its band structure and DOS map. (c) (9,0) and (0,9) 6,6,2-GNTs Fig.2: The Fermi velocities around the Dirac points (DP) as functions of tube radius. Keywords: graphyne nanotube; Young's modulus; electronic structures; Dirac point References: [] Yang D. C.; Jia R.; Zhang H. X.; J. Phy. Chem. C 207, 2: 4835-4844. [2] Lu J. P.; Phys. Rev. Lett. 997, 79: 297. [3] Puigdollers, A. R.; Alonso, G., Gamallo, P.; Carbon. 206, 96: 879. [4] Malko, D.; Neiss, C.; Viñes, F.; Görling, A.; Phys. Rev. Lett. 20, 08: 086804. 329

P-4-044 Nonadiabatic Curve-crossing Model for Single Electron Transfer in Visible-Light Photoredox Catalysis Wenjing Yang, Xuebo Chen 2,* Department of Material Science & Engineering, Taiyuan University of Technology, Shanxi Province Ying-ze-da-jie No. 79, Taiyuan 030024. 2* Key Laboratory of Theoretical and Computational Photochemistry of Ministry of Education, Department of Chemistry Beijing Normal University Xin-wai-da-jie No. 9, Beijing 00875. *Email: xuebochen@bnu.edu.cn Photoredox catalysis relies on excited-state single-electron transfer(set) processes to drive unique photochemical reactions. In this work, accurate electronic structure calculations at the CASPT2//CASSCF/PCM level of theory are employed to provide new insights into the SET initiation, activation, and deactivation in the photoredox α-vinylation reactions mediated by iridium (III) catalysts. A nonadiabatic curve-crossing model, in essence of Marcus electron transfer theory, is established for the mechanistic description of the SET events. It was found that the catalytic cycle is triggered by the metal-to-ligand charge transfer (MLCT) excitation of the catalysts and the subsequent photo-induced dipole-dipole interaction brings about the initial α-c-h functionalization of the amine substrate. The final C-C bond construction proceeds in a concerted fashion with the departure of the protonated leaving group. The calculations demonstrate that the catalytic efficiency can be controlled by the nuclear reorganization for the SET process, which is associated with amine planarization in the crossing region of the metal-based redox paths. These mechanistic insights offer a plausible picture for the excited-state SET-mediated chemical transformations that should be applicable to further studies of photoredox catalysis in organic chemistry Photoredox catalysis relies on excited-state single-electron transfer (SET) processes to drive a series of unique bond-forming reactions. A nonadiabatic curve-crossing model, in essence of Marcus electron transfer theory, is first established for the mechanistic description of the SET initiation, activation, and deactivations by calculating the SET paths for a paradigm example of photoredox α-vinylation reaction mediated by iridium (III) catalysts. This SET model should be applicable to further studies of photoredox catalysis in organic chemistry. Keywords: Photoredox catalysis; SET; Marcus electron transfer theory References: [] Noble, A.; MacMillan, D. W. C. J. Am. Chem. Soc. 204, 36: 602. [2] Wang, H. J.; Cao, X. Y.; Chen, X. B.; Fang, W. H.; Dolg, M. Angew. Chem. Int. Ed. 205, 54: 4295. [3] Marcus, R. A. Annu. Rev. Phys. Chem. 964, 5: 55. 330

P-4-045 Deep learning for pharmaceutical formulation prediction Yilong Yang, Zhuyifan Ye, Yan Su, Jing Jing, Qianqian Zhao, Defang Ouyang,* State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences (ICMS), University of Macau, Macau, China *Email: defangouyang@umac.mo [Background] Today formulation development still strongly relies on the traditional trial-and-error approach by individual experiences of pharmaceutical scientists, which is laborious, time-consuming and cost-expensive. [Aim] The aim of this research is to use deep learning to predict pharmaceutical formulations. [Method] Three different types of dosage forms were selected as the model systems, including solid dispersion (SD), oral fast disintegrating films (OFDF), and sustained release matrix tablets (SRMT). 00-200 data of each system were extracted from the database Web of Science. [Results] One of the main difficulties in pharmaceutical prediction is the small data set with imbalanced input space due to the limited experimental data. Automated testing set selection method was developed for the selection of the representative dataset. Moreover, specific evaluation criteria in pharmaceutics were applied to assessing the accuracies of the three deep learning models. After the training of multiple layers feed forward neural network, the accuracies of all three models were above 75%, which showed good prediction in pharmaceutical formulations. [Conclusion] In summary, the deep neural network with the automated data set selection algorithm was firstly developed for the prediction of pharmaceutical formulations. This approach also could be applied to other drug delivery systems. Step 2: select initial set w ith m inim um distance Final initial Set Testing Set Step : get rid of sm all group Pharmacetical Data Step 3: Repeatedly pickup data w ith m axim um cost Sm all G roup Filter Remaining Set Traning Set M D-FIS Figure MD-FIS algorithm Keywords: pharmaceutical formulation, deep learning, small dataset, solid dispersion, oral fast disintegrating film, and sustained release matrix tablet 33

P-4-046 Elucidating the host-guest binding mechanisms by the molecular dynamics/quantum mechanics/continuum solvent model approach Renlong Ye, Baojing Zhou * Computational Institute for Molecules and Materials, School of Chemical Engineering, Nanjing University of Science and Technology, Xiaolingwei 200, Nanjing 20094, China *Email: bzhou@mail.njust.edu.cn We introduce a molecular dynamics/quantum mechanics/continuum solvent model (MD/QM/CSM, Ye et al. in Chem. Phys. Lett., 206, 648: 70) to investigate the microscopic binding mechanisms of host-guest systems. The key components of the MD/QM/CSM approach include the generation of the representative host-guest binding conformations from MD simulations and binding affinity computations via the QM/CSM model. When applied to various cyclodextrin supermolecule systems,2, the major binding modes are revealed. Moreover, combined with experimental data, the roles of host-guest interactions and solvent effects in determining the binding thermodynamics are elucidated, which provides new insight into the binding mechanism. Keywords: MD/QM/CSM approach; host-guest system; binding affinity References: [] Ye, R.; Nie, X.; Zhou, Y.; Wong, C. F.; Gong, X.; Jiang, W.; Tang, W.; Wang, Y. A.; Heine, T.; Zhou, B. Chem. Phys. Lett. 206, 648: 70. [2] Dang, P.; Ye, R.; Meng, F.; Han, Y.; Zhou, Y.; Gong, X.; Zhou, B. J. Incl. Phenom. Macrocycl. Chem. 207, 88: 8. 332

P-4-047 不同力场对 DNA 构型转变的影响 * 张宏, 邵学广, 蔡文生 南开大学化学学院, 分析科学研究中心, 天津市卫津路 94 号,30007 *wscai@nankai.edu.cn DNA 等生物大分子的结构改变与生命活动息息相关, 分子动力学模拟的方法被广泛应用于探究生物分子的微观结构变化, 而分子动力学模拟的准确性极大程度上依赖于分子力场的精确程度 对于生物大分子而言,CHARMM AMBER GROMOS OPLS 等力场发展已经较为成熟 对于 DNA 而言, 应用较广泛的力场包括 CHARMM 和 AMBER 力场 [] 为了探究常用力场对 DNA 构象描述的精确程度, 本文分别使用了 CHARMM 和 AMBER 力场对 B-DNA 到 A-DNA 的构型转变进行了模拟, 并使用自由能计算的方法计算了 B-DNA 到 A-DNA 转变的自由能变化 [2] 结果表明对 AT/CG 碱基序列,CHARMM 和 AMBER 力场将会导向不同的稳定结构, 并且有着完全不同的 B-DNA 到 A-DNA 反应路径和自由能变化 并且这两种力场所得结果均不能与实验吻合 本文的结果可以为今后的分子模拟实验设计提供理论指导, 并且对进一步的参数优化提供帮助 关键词 :B-DNA;A-DNA;CHARMM;AMBER; 力场比较 参考文献 [] Galindo-Murillo, R.; Robertson, J. C.; Zgarbova, M.; Sponer, J.; Otyepka, M.; Jurecka, P.; Cheatham, T. E., 3rd, J. Chem. Theory Comput.206, 2: 44. [2] Fu, H.H.; Shao, X.G.; Chipot C.; Cai, W.S, J. Chem. Theory Comput. 206, 2: 3506. 国家自然科学基金项目 (No. 23737) 资助 333

P-4-048 DFT Study on C-H Amination Reactions Catalyzed by Iron Porphyrin Nitrene Compounds with Different Nitrogen Sources Jiahua Zhang, Cheng Hou, Huiying Xu* and Cunyuan Zhao* MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, Sun Yat-Sen University, Guangzhou 50275 (P. R. China) E-mail: ceszhcy@mail.sysu.edu.cn Metalloporphyrin nitrene compounds have been engineered to catalyze C-H amination reactions. Iron as a cheap metal source and two substituent of nitrogen source (R= -CH3 and -SO3H)had been utilized to study how different nitrogen sources affects the process of C-H amination catalyzed by iron porphyrin nitrene. The R substituent effects in the mechanism of saturated C-H amination catalyzed by R= -CH3 and -SO3H iron porphyrin nitrene are investigated by a DFT approach. The strong electron-withdrawing R substituent leads to a high-spin stepwise C-H amination reaction with lower activation barrier than the weak electron-withdrawing R substituent. The rate-determining step in the C-H amination is the H-abstraction process. [] And strong electron-withdrawing R substituent significantly influences the electronic property of metal iron and the close examination on the spin density of nitrene N suggests mix-spin transition states exist in high-spin quintet reactions. The theoretical observations presented in the paper propose that strong electron-withdrawing substituent nitrogen source is in favor of C-H amination reactions catalyzed by iron porphyrin nitrene. Fig. The mechanism of C-H amination reactions Keywords: metalloporphyrin; nitrene; C-H amination; DFT; reactional mechanism References: [] Xuepeng Zhang, Huiying Xu, and Cunyuan Zhao, J. Org. Chem. 204, 79, 9799-98. 334

P-4-049 Theoretical Insight into C(sp 3 )-F Bond Activations and Origins of Chemo- and Regioselectivities of Tunable Nickel-Mediated/Catalyzed Couplings of 2-Trifluoromethyl--alkenes with Alkynes Xiaomin Zhang, Yuxia Liu,* Guang Chen, Guojing Pei and Siwei Bi School of Chemistry and Chemical Engineering, Qufu Normal University, Qufu 27365, P.R. China, liuyuxia2008@63.com; siweibi@26.com Abstract Organic fluorine compounds such as freon, fluoro-liquid crystals, optical fiber, poly(tetrafluroethylene) (PTFE), pharmaceuticals and agrochemicals etc., have received great interest and attention in diverse fields of science due to their own unique properties that are difficultly obtained from other organic compounds []. Compared with transition-metal-mediated C-F bond activation of aryl and vinyl fluorides [2], the C-F bond activation of the trifluoromethyl group remains a great challenge, which might not only be attributed to the high chemical stability of the C(sp3)-F bond but also because of the strong shielding effect of the lone-pair electrons on three F atoms [3]. Recently, Ichikawa and co-workers developed the Ni(cod)2/PCy3-mediated selective coupling reactions of 2-trifluoromethyl--alkenes and 4-octyne in toluene, which were demonstrated to be available under relatively mild conditions. On the basis of the calculated results, we uncovered (i) the origin of selectively cleaving two C(sp 3 )-F bonds of the trifluoromethyl group in the stoichiometric reaction, (ii)the intrinsic reasons for the Et3SiH-dominated chemoselectivity, and (iii) the respective roles of ZnMe2 and AlMe3 in dominating the product-divergence. The present theoretical results not only rationalize the experimental observations but provide insight into the mechanism details of the significant Ni-mediated coupling reactions. Keywords: nickel, C(sp 3 )-F activation, DFT, divergent regioselectivity, chemo-selectivity, 2-trifluoromethyl--alkenes, alkynes References Thomas, Hayden P.; Wang, Yue-Ming.; Lorenzini, Fabio.Organometallics. 207, 36, 960-963. Tobisu, M.; Xu, T.; Shimasaki, T.; Chatani, N.J. Am. Chem.Soc. 20, 33, 9505 95. Stahl, T.; Klare, H. F. T.; Oestreich, M. ACS Catal. 203, 3, 578-587. 335

P-4-050 光诱导电子转移调控的双催化 [2+2] 环加成反应机理研究张晓蕊,*, 陈雪波 北京师范大学化学学院, 理论与计算光化学教育部重点实验室, 北京市新街口外大街 9 号,00875 *Email: xuebochen@bnu.edu.cn 催化反应是当代合成化学的核心和基础, 以 Ru(II) 为代表的光催化剂能够有效吸收可见光, 产生兼具强氧化性和还原性的激发态中间体, 提供与传统氧化还原反应完全不同的反应环境, 实现 绿色 合成 对于其中涉及的复杂的电子转移过程和不对称诱导机制, 尚仅窥得一斑 我们运用多组态微扰理论, 发展适于光催化反应的光诱导电子转移数值模拟方案, 研究 Ru(bpy)3Cl2 可见光催化剂和手性 Lewis 酸催化剂调控的烯酮 [2+2] 环加成反应机理 主要科学发现如下 :() 背景反应 : 苯基丙烯酮在紫外光激发下到达 ππ* 态, 可在激发单态弛豫, 到达基态后结合另一烯酮底物生成外消旋 [2+2] 环加成产物, 但基态反应能垒较高 ; 同时, 底物亦可从激发单态系间窜跃到 3 ππ* 态, 得到双自由基中间体, 与丁烯酮反应, 同样生成外消旋产物 (2) 手性 Lewis 酸调控的催化反应 : 与手性 Lewis 酸催化剂的配位作用, 可调节苯基丙烯酮底物的激发态能级顺序, 显著提高其 nπ* 跃迁能量 降低 ππ* 跃迁能量, 且重原子 Eu(III) 的参与提高自旋轨道相互作用, 加速底物系间窜跃的发生, 从而提高催化反应的立体选择性 ; (3) 钌复合物光催化剂敏化 手性 Lewis 酸不对称诱导的双催化反应 : 可见光照射下 Ru(bpy) 3 2+ 到达 3 dπ* 后被 i-pr2net 还原, 苯基丙烯酮底物 π* 轨道可从 Ru(bpy)3 + 光催化剂得到电子, 生成自由基中间体, 进而与另一烯酮底物成键 ; 而后反应体系的电子又回到失去电子的还原剂, 最终高产率 高对映选择性地生成环丁烷产物 通过我们的计算, 结合光催化最低能量反应势能面和 Marcus 电子转移理论模型, 提出了双催化体系激发态能量调控和立体选择性控制机制 关键词 : 多组态微扰理论 ; 光催化 ; 电子转移 ; 对映选择性 ; 环加成 参考文献 []Du, J.; Skubi, K. L.; Schultz, D. M.; Yoon, T. P. Science 204, 344: 392. [2]Prier, C. K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 203, 3: 5322. [3]Wang, H. J.; Cao, X. Y.; Chen, X. B.; Fang, W. H.; Dolg, M. Angew. Chem. Int. Ed. 205, 54: 4295. [4]Wang, H. J.; Fang, W. H.; Chen, X. B.; J. Org. Chem. 206, 8: 7093. [5]Du, J.; Yoon, T. P. J. Am. Chem. Soc. 2009, 3: 4604. [6]Ischay, M. A.; Anzovino, M. E.; Du, J.; Yoon, T. P. J. Am. Chem. Soc. 2008, 30: 2886. 336

P-4-05 压差驱动下水和离子穿越碳纳米管的输运行为 赵云震, 方昶, 吕福静, 苏加叶,* 南京理工大学, 南京市孝陵卫 200 号,20094 *Email: jysu@iccas.ac.cn 水和离子在生命活动中有着不可或缺的作用, 过去十年里, 大量的模拟 [-3] 和实验 [4-5] 工作已经证明了水分子在碳纳米管中输运拥有不同于在传统通道输运的特殊表现 这项工作中, 我们通过使用分子动力学模拟的方法系统分析了离子条件对水和离子在压力驱动下共同通过碳纳米管的影响, 例如盐溶液种类以及离子浓度都可以明显调节离子以及水分子的输运 与传统流体力学运动方程预测的结果一致, 离子和水分子流量与压力成线性关系, 而且各系统中阴离子与阳离子流量呈一定比例 随着压力增加, 离子和水分子输运时间都减少,LaCl 3 系统中离子和水分子输运时间出现一个最大值, 同时, 我们可以发现每个系统中阴离子和阳离子的平均输运时间几乎相等 随着盐溶液浓度的增加, 水分子流量减少, 但离子流量出现一个最大值, 离子和水分子的平均输运时间都是增加的 我们模拟的结果揭示了压力驱动下离子和水耦合输运的规律, 特别是离子条件对于输运的影响, 这对以后设计离子和水输运器件以及研究生命体中离子和水的跨膜运输都有一定的参考意义 Fig. Simulation snapshot and ion flux as a function of pressure. 关键词 : 水分子 ; 输运 ; 碳纳米管 参考文献 [] De Groot, B. L.; Grubmuller, H. Science 200, 294: 2353. [2] Hummer, G.; Rasaiah, J. C.; Noworyta, J. P. Nature 200, 44: 88. [3] Sisan, T. B.; Lichter, S. Phys. Rev. Lett. 204, 2: 04450. [4] Holt, J. K.; Park, H. G.; Wang, Y. M.; et al. Science 2006, 32: 034. [5] Secchi, E.; Marbach, S.; Nigues, A.; et al. Nature 206, 537: 20. 337

P-4-052 Exploration of the ph-induced misfolding mechanism of prion protein: insight from molecular dynamics simulations and Markov state model analysis Shuangyan Zhou, Xiaojun Yao 2, Huanxiang Liu,* School of Pharmacy, Lanzhou University, Lanzhou 730000 2 State Key Laboratory of Applied Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000 *Email: hxliu@lzu.edu.cn The misfolding and aggregation of prion protein into its misfolded forms are associated with several neurodegenerative diseases. Thus, understanding the misfolding mechanism of prion protein is the fundamental to effective treatment of related prion diseases. In the present study, by performing molecular dynamics simulation, we explored the potential misfolding mechanism of prion protein under the acidic environment, which is known to accelerate and trigger misfolded oligomer formation of prion.[-2] Our obtained results reveal that at acidic ph, the globular domain of prion protein is partially unfolded, especially the α2 C-terminus. By Markov state model analysis, we identified two large conformational states S8 and S9 with disrupted native structure and two macrostates S2 and S3 with extended native β-sheet and newly formed β-strands but low equilibrium probability. Moreover, from a defined near native state S7, the formation time scale of S8 is quite short on microseconds scale while the formation of S2 and S3 is relative long on milliseconds scale. We thus conclude at acidic ph, human prion protein is easier to misfolded into partially unfolded isoform but energy stable states rather than states with extended native β-sheet and β-rich conformers.[3] Deep structural analysis of conformational states indicates that in the acidic environment, protonation of H87 which buries into the native structure is the main cause for the early prion misfolding at acidic environment. On one hand, protonation of H87 increases the electrostatic repulsion with R56, and thus disrupt the residue connections with α-β2 loop. On the other hand, protonation of H87 increases the hydrophilic of it and the increased hydrophilic drives H87 expose to solvent leading to hydrophobic residue F98 escaping from hydrophobic core. Taken these two aspects together, protonation of H87 greatly increases the structural flexible, especially the α2 C-terminus. As a whole, we infer that the α2 C-terminus may play a vital important role in the early misfolding stage and this region may serve as a potential molecular target in drug designing for prion disease. Key words: prion protein misfolding; acidic ph; molecular dynamics simulation; Markov state model Reference: [] Singh, J.; Udgaonkar, J. B. J. Mol. Biol. 206, 428:345. [2] Van der Kamp, M. W.; Daggett, V. Biophys. J. 200, 99: 2289. [3] Singh, R. K.; Chamachi, N. G.; Chakrabarty, S.; Mukherjee, A. J. Phys. Chem. B. 207, 2:550. 338

P-4-053 DFT Study on the Mechanistic Insights into the Hydrolysis of BNPP Catalyzed by Mononuclear zinc Complexes Xiaoyu Zhou, Xuepeng Zhang, Cunyuan Zhao* School of Chemistry, Sun Yat-Sen University, Guangzhou 50275 *ceszhcy@mail.sysu.edu.cn Metal-ion-coordinated nucleophiles plays important role in developing artificial metal to cleave DNA. Recent developments of intramolecular nucleophile have attracted much attention. In contrast to current general mechanistic explanations, the intramolecular nucleophile has been prevented binding to the metal ion, withing a more effective Lewis acid and more reactive nucleophile. Recently, Williams group s experiments confirm that the mononuclear Zn complex incoporated oxime ligand is the most reactive intramolecular nucleophile than the complexes of acetal hydrate and alkoxide toward BNPP cleavage. [, 2] Intramolecular nucleophile is effective strategy for metal-ion-coordinated nucleophiles, however, it is noteworthy that what are the effects of different ligands on the pka values and the atomic charge distribution and what is the reaction mechanism of the hydrolytic process. Fig. The hydrolytic process of mononuclear zinc complex.. Keywords: DFT, mononuclear zinc complex, nucleophile, the reaction mechanism References: [] Tirel, E. Y; Bellamy, Z.; Adams, H.; Lebrun, V.; Duarte, F.; Williams,N.H. Angew. Chem. 204, 26:8385. [2] Tirel, E. Y; Williams,N.H. Chem. Eur.J. 205, 2:7053. 339

主办 : 中国化学会 承办 : 计算机化学专业委员会 南京大学化学化工学院 协办 : 南京大学理论与计算化学研究所 配位化学国家重点 实验室 生命分析国家重点实验室 高性能高分子材料与技 术教育部重点实验室和江苏省化学化工学会 支持单位 :AIP Publishing 北京并行科技股份有限公司广州景派科技有限公司梅特勒 - 托利多国际贸易 ( 上海 ) 有限公司 340