毕业论文_抗结核病药物的3D-QSAR定量结构性质关系研究.doc

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)对个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(Multiple linear regression MLR)及偏最小二乘回归(partial least square regression 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。3D-HoVAIF 的MLR及PLS建模的复相关系数(Rcum2)、留一法(leave-one-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结果表明，3D-HoVAIF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定量构效关系Anti-TB drugs by 3D-QSAR Quantitative Structure-Property Relationship Study ABSTRACT A newly developed three-dimensional holographic vector of atomic interaction field (3D-HoVAIF) and Protein-based virtual surface receptor molecule atom probe analysis of random sampling (RaSMS) were used to describe the chemical structures of 25 Chalcone as antituberculosis agents. Here quantitative structure activity relationship (QSAR) models were built by Multiple linear regression （MLR） and partial least square regression (PLS). The estimation stability and generalization ability of these models were strictly analyzed by both internal and external validations. 3D-HoVAIF, the correlation coefficient (R2) of established MLR and PLS， leave-one-out (LOO) cross-validation (CV) predicted values versus experimental ones of external samples were 0.998、0.9、0.9 and 0.926、0.、0. respectively. When use (RaSMS), the results were 0951、、、、 results indicated that results of PLS here had favorable estimation stability and good prediction capabilities. Satisfactory results showed that 3D-HoVAIF and RaSMS could preferably express information related to biological activity of anti-tuberculosis drug. KEY WORDS: in vitro antibacterial activity, anti-tuberculosis drug, three-dimensional holographic vector of atomic interaction field, quantitative (3D-HoVAIF), Protein-based virtual surface receptor molecule atom probe analysis of random sampling (RaSMS), structure-activity relationship (QSAR) 目 录 I ABSTRACT II 1 引 言 1 1.1 结核病和抗结核病药物简介 1 1.1.1 结核病简介 1 1.1.2 抗菌活性 1 1.