分子模拟

,浅谈Molecular Simulation Technology：Materials Studio and Discovery Studio,Nanchang University,2016-12-19,Instroduction：Discovery Studio,1. PC上拥有全新的分子建模环境，专业的生命科学分子模拟软件。2.以生物大分子（蛋白、核酸、多糖）和有机小分子为研究对象，应用学科涵盖生命科学、药物化学等领域。3.功能：分子对接、药效团、片段设计、QSAR、ADMET、虚拟组合库、分子动力学、同源建模、蛋白对接、蛋白设计等。4.算法：LigandFit、CDOCKER、HypoGen、HipHop、Ligandscout、LUDI、Breed、MODELER、ZDOCK、CHRMm等。5.支持Windows和Linux系统。,DS 操作界面,分子对接就是两个或多个分子之间通过几何匹配和能量匹配而相互识别的过程，它是把配体分子放在受体活性位点的位置，然后按照几何互补、能量互补和化学环境互补的原则来实时评价配体与受体相互作用的优良，并找到两个分子之间最佳的结合模式。,Molecular Docking,锁钥模型,诱导契合模型,刚性对接,柔性对接,刚性对接：配体受体均为刚性,柔性对接：配体受体均为柔性,半柔性对接,CDOCKER是基于CHARMm力场的精准的分子对接技术（半柔性对接）,Discovery Studio CDOCKER,Molecular Docking,PPO-Apigenin,Xiong Z, Liu W, Zhou L, et al. Mushroom (Agaricus bisporus) polyphenoloxidase inhibited by apigenin: Multi-spectroscopic analyses and computational docking simulationJ. Food chemistry, 2016, 203: 430-439.,PPO-Apigenin Interaction,Xiong Z, Liu W, Zhou L, et al. Mushroom (Agaricus bisporus) polyphenoloxidase inhibited by apigenin: Multi-spectroscopic analyses and computational docking simulationJ. Food chemistry, 2016, 203: 430-439.,Apigenin interacted with various amino acid residues including His61, His85, His244, His259, Asn260, His263, Phe264, Met280, Gly281, Ser282, Val283, Ala286 and Phe292.,Zhou D, Li L, Wu Y, et al. Salicylic acid inhibits enzymatic browning of fresh-cut Chinese chestnut (Castanea mollissima) by competitively inhibiting polyphenol oxidaseJ. Food chemistry, 2015, 171: 19-25.,Tiwari M, Lee J K. Molecular modeling studies of L-arabinitol 4-dehydrogenase of Hypocrea jecorina: its binding interactions with substrate and cofactorJ. Journal of Molecular Graphics and Modelling, 2010, 28(8): 707-713.,Instruction：Materials Studio,1.Materials Studio是专门为材料科学领域研究者开发的一款可运行在PC上的模拟软件。2.多种先进算法的综合应用使MS成为一个强大的模拟工具。无论构型优化、性质预测和X射线衍射分析，还是复杂的动力学模拟和量子力学计算。3.模拟的内容包括了催化剂、聚合物、固体及表面、晶体与衍射、化学反应等材料和化学研究领域的主要课题。4.计算模块（如Discover，Amorphous，Equilibria，DMol3，CASTEP等）运行于服务器端，支持的系统包括Windows2000、NT、SGIIRIX以及Red Hat Linux。,MS 操作界面,Molecular Dynamics,Molecular Dynamics,Molecular Dynamics,分子动力学原理,初始位置和速度,第二次位置和速度,获取单体结构,构建聚合物,搭建模型,退火,动力学平衡,动力学模拟,结果分析,分子动力学步骤,Experimental Program,Background,-cyclodextrin and H2O,-cyclodextrin containing 10% w/w H2O,Energy minimized structure of -cyclodextrin containing 10% w/w H2O,hydrogen bonding (blue dotted bonds),Zhou G, Zhao T, Wan J, et al. Predict the glass transition temperature and plasticization of -cyclodextrin/water binary system by molecular dynamics simulationJ. Carbohydrate research, 2015, 401: 89-95.,Experimental Program,Figure 1. Simulated amorphous cells of -cyclodextrin containing (a) 0% (b) 3% (c) 5% and (d) 10% w/w water; water molecules are shown in red, and -cyclodextrin molecules are shown in green,Forcite Module,Atom, Volumes and Suarfce Module,Discover Module + Free Volume Theory,Glass Transition Ttemperature,Radial distribution function &Diffusion coefficient,Fractional free volume,Experimental Program,径向分布函数：共混体系中组分分子链之间的C-C原子对的径向分布函数能够表征共混体系的相容性，径向分布函数越大，相容性越好。自由体积：聚合物体积由高分子占有体积与未被高分子占有的以“空穴”形式存在的自由体积所组成。自由体积提供了必要的活动空间和分子扩散的空间。,Experimental Results,Table 1. Comparison of glass transition temperatures for -CD/H2O binary system,Fox equat