抗结核病药物的3d-qsar定量结构性质关系研究 毕业论文

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1、III抗结核病药物的3D-QSAR定量结构性质关系研究摘要采用三维全息原子场作用矢量(3D-HoVAIF)和基于虚拟蛋白质受体原子探针的分子表面随机采样分析(RaSMS)对25个查耳酮类抗结核病药物进行定量构效关系(QSAR)研究。运用多元线性回归(Multiplelinearregression,MLR)及偏最小二乘回归(partialleastsquareregression,PLS)建模，同时采用内部及外部双重验证的办法对所得模型稳定性能进行了深入分析和检验。采用3D-HoVAIF的MLR及PLS建模的复相关系数(Rcum2)、留一法(leave-on

2、e-out,LOO)交互校验(cross-validation,CV)复相关系数(QLOO2)和外部样本校验复相关系数(Qext2)分别为0.984、0.920、0.808和0.998、0.975、0.903；采用RaSMS分别为0.975、0.914、0.764和0.926、0.905、0.829。结果表明，3D-HoVAIF和RaSMS都有较好表征抗结核药物分子结构信息，因而能建立具有良好稳定性和预测能力的QSAR模型。关键词：体外抗菌活性，抗结核病药物，三维全息原子场作用矢量，比较分子/虚拟受体相互作用分析法，定量构效关系IIIAnti-TBdrugs

3、by3D-QSARQuantitativeStructure-PropertyRelationshipStudyABSTRACTAnewlydevelopedthree-dimensionalholographicvectorofatomicinteractionfield(3D-HoVAIF)andProtein-basedvirtualsurfacereceptormoleculeatomprobeanalysisofrandomsampling(RaSMS)wereusedtodescribethechemicalstructuresof25Chalc

4、oneasantituberculosisagents.Herequantitativestructureactivityrelationship(QSAR)modelswerebuiltbyMultiplelinearregression（MLR）andpartialleastsquareregression(PLS).Theestimationstabilityandgeneralizationabilityofthesemodelswerestrictlyanalyzedbybothinternalandexternalvalidations.When

5、use3D-HoVAIF,thecorrelationcoefficient(R2)ofestablishedMLRandPLS，leave-one-out(LOO)cross-validation(CV),predictedvaluesversusexperimentalonesofexternalsampleswere0.998、0.975、0.903and0.926、0.785、0.785,respectively.Whenuse(RaSMS),theresultswere0951、0.914、0.829and0.928、0.905、0.764.The

6、resultsindicatedthatresultsofPLSherehadfavorableestimationstabilityandgoodpredictioncapabilities.Satisfactoryresultsshowedthat3D-HoVAIFandRaSMScouldpreferablyexpressinformationrelatedtobiologicalactivityofanti-tuberculosisdrug.KEYWORDS:invitroantibacterialactivity,anti-tuberculosis

7、drug,three-dimensionalholographicvectorofatomicinteractionfield,quantitative(3D-HoVAIF),Protein-basedvirtualsurfacereceptormoleculeatomprobeanalysisofrandomsampling(RaSMS),structure-activityrelationship(QSAR)III目录摘要IABSTRACTII1引言11.1结核病和抗结核病药物简介11.1.1结核病简介11.1.2抗菌活性11.1.3抗结核病药物的发展历

8、史11.1.4抗结合药物回顾21.1.5抗结核新药研