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《抗結(jié)核病藥物的3d-qsar定量結(jié)構(gòu)性質(zhì)關(guān)系研究 畢業(yè)論文》由會員上傳分享，免費在線閱讀，更多相關(guān)內(nèi)容在學術(shù)論文-天天文庫。
1、III抗結(jié)核病藥物的3D-QSAR定量結(jié)構(gòu)性質(zhì)關(guān)系研究摘要采用三維全息原子場作用矢量(3D-HoVAIF)和基于虛擬蛋白質(zhì)受體原子探針的分子表面隨機采樣分析(RaSMS)對25個查耳酮類抗結(jié)核病藥物進行定量構(gòu)效關(guān)系(QSAR)研究。運用多元線性回歸(Multiplelinearregression,MLR)及偏最小二乘回歸(partialleastsquareregression,PLS)建模，同時采用內(nèi)部及外部雙重驗證的辦法對所得模型穩(wěn)定性能進行了深入分析和檢驗。采用3D-HoVAIF的MLR及PLS建模的復相關(guān)系數(shù)(Rcum2)、留一法(leave-on
2、e-out,LOO)交互校驗(cross-validation,CV)復相關(guān)系數(shù)(QLOO2)和外部樣本校驗復相關(guān)系數(shù)(Qext2)分別為0.984、0.920、0.808和0.998、0.975、0.903；采用RaSMS分別為0.975、0.914、0.764和0.926、0.905、0.829。結(jié)果表明，3D-HoVAIF和RaSMS都有較好表征抗結(jié)核藥物分子結(jié)構(gòu)信息，因而能建立具有良好穩(wěn)定性和預測能力的QSAR模型。關(guān)鍵詞：體外抗菌活性，抗結(jié)核病藥物，三維全息原子場作用矢量，比較分子/虛擬受體相互作用分析法，定量構(gòu)效關(guān)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目錄摘要IABSTRACTII1引言11.1結(jié)核病和抗結(jié)核病藥物簡介11.1.1結(jié)核病簡介11.1.2抗菌活性11.1.3抗結(jié)核病藥物的發(fā)展歷
8、史11.1.4抗結(jié)合藥物回顧21.1.5抗結(jié)核新藥研
