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1、单击此处编辑母版标题样式MolecularDynamicssimulationin•单击此处编辑母版文本样式drugdiscovery•第二级•第三级吕炜•第四级创腾科技公司•第五级什么是分子动力学？•目前分子模拟技术中最常单击此处编辑母版标题样式用的方法•用动态的模拟方法揭示生物学的奥秘•可以用于药物设计研究以单击此处编辑母版副标题样式及蛋白-结构功能研究分子动力学的发展历史：ThefirstMDsimulationofaproteinA9.2pstrajectoryforaMcCammon,J.A.,Gelin,B.R.&smallproteininvacuumKarpl
2、us,M.(1977)Nature267,585–590.A210pssimulationof单击此处编辑母版标题样式Levitt,M.&Sharon,R.(1988)thesameproteininProc.Natl.Acad.waterSci.USA85,7557–7561.Theincreaseincomputingpower单击此处编辑母版副标题样式ImprovementinthepotentialfunctionsMuchlargerproteins1,000-10,000timesaslongastheoriginalsimulation(10-100ns)Wat
3、erandsaltconditions单击此处编辑母版标题样式单击此处编辑母版副标题样式单击此处编辑母版标题样式单击此处编辑母版副标题样式分子动力学的应用：单击此处编辑母版标题样式单击此处编辑母版副标题样式•蛋白折叠研究•蛋白模型优化•酶催化反应机理研究•配体-受体诱导契合研究•蛋白结构与功能关系研究•自由能计算研究◆Misfoldingisinvolvedinarangeofdisease.Dobson,C.M.(2003)Nature426,884–890.◆Howdoesaproteinfold?◆Problem!FoldingisslowProteinfolding(
4、Eventhefastestproteintakemicrosecondstofold)◆SimplifiedmodelsareusedinsimulationoffoldingMentoCarlodynamicsSimplifiedbeadmodelsonacubiclatticeDobson,C.M.,Sali,A.&27-beadpolymertonativestateKarplus,M.(1998)Manyordersshorterthanrequired(~5×10steps----Angew.Chem.37,868–---10possibleconfigurati
5、ons7893.Generallyacceptedasthe16solutionofthesearchprobleminproteinfolding单击此处编辑母版标题样式单击此处编辑母版副标题样式DiscretemoleculardynamicsalgorithmsZhou,Y.&Karplus,M.(1999)Nature401,400–403.Itislikelythatwithinthenext10yearsabinitiofoldingwillreachthestageatwhichitcanbeusednotonlytodeterminethedetailsoft
6、hefoldingmechanismbutalsotoaidinsolvingthe单击此处编辑母版标题样式‘‘other’’foldingproblem,thatofdeterminingthestructureofthenativestatedirectlyfromthesequencebymoleculardynamicssimulations.单击此处编辑母版副标题样式EnzymecatalysisQM/MM单击此处编辑母版标题样式单击此处编辑母版副标题样式MolecularMechanicalQuantumMechanicalATPHydrolysisbyMyosi
7、n单击此处编辑母版标题样式单击此处编辑母版副标题样式Futureprospects•Transitionpathbetweenlowenergyregion----energybarriers•ExperimentstructurebiologistuseMDProduct•Reactionpathsearchmethodsand单击此处编辑母版标题样式improvedtreatmentofsolventbyimplicitReactantmethod单击此处编辑母版副标题样式MDinstructure
