三维全息原子场作用矢量用于5′-甲硫腺苷核苷酶抑制剂的定量结构-活性相关研究  

QSAR Studies of 5′-methylthioadenosine Nucleosidase Inhibitors Using Three-Dimensional Holographic Vector of Atomic Interaction Field

作　　者：李美萍[1] 张生万[1] 

机构地区：[1]山西大学生命科学学院,山西太原030006

出　　处：《分析科学学报》2011年第5期566-572,共7页Journal of Analytical Science

基　　金：山西省回国留学人员科研项目(No.200902)

摘　　要：采用三维全息原子场作用矢量(Three-dimensional Holographic Vector of Atomic Interaction Field,3D-HoVAIF)对33个5′-甲硫腺苷核苷酶抑制剂进行结构表征并与其抑制活性建立定量结构-活性相关(Quantitative Structure Activity Relationship,QSAR)模型。分别采用多元线性回归(MLR)和偏最小二乘回归(PLS)进行建模,同时采用内部及外部双重验证的方法对所建模型稳定性能进行分析和验证,建模计算值、留一法交互检验预测值和外部样本预测值的复相关系数R、Rcv、Qext分别为0.874,0.773,0.953(MLR);0.873,0.727,0.952(PLS)。表明三维全息原子场作用矢量能较好地表征该类分子的结构信息,所建QSAR模型具有良好的稳定性和预测能力;同时也指出了sp3杂化的C原子与sp2杂化的N原子,以及sp3杂化的C原子与sp3杂化的O/S原子的静电作用是影响5′-甲硫腺苷(MTA)类似物抑制5′-甲硫腺苷核苷酶(MTAN)活性的重要因素,有望对其它5′-甲硫腺苷核苷酶抑制剂的抑制活性预测及合成MTA类似物提供有效的理论依据。Three-dimensional holographic vector of atomic interaction field（3D-HoVAIF）was used to describe the structure of 5′-methylthioadenosine nucleosidase（MTAN）inhibitors.Quantitative structure-activity relationship（QSAR）between the 3D-HoVAIF parameters and activity of 5′-methylthioadenosine nucleosidase inhibitors was generated by multiple linear regression（MLR）and partial least square regression（PLS）with variable screening by the stepwise multiple regression technique and statistics.The correlation coefficient R of established MLR and PLS models,leave-one-out（LOO）cross-validation（CV）,Qext were 0.874,0.773,0.953（MLR）;0.873,0.727,0.952（PLS）,respectively.The result showed that 3D-HoVAIF was applicable to the molecular structural characterization and the model had favorable stability and good prediction capabilities.In addition,the result disclosed the influence of the key factors on MTAN inhibitors activity,and the model would also provide valid theoretical basis for predicting activity of other MTAN inhibitors.

关 键 词：三维全息原子场作用矢量 5′-甲硫腺苷核苷酶抑制剂 定量结构-活性相关 

分 类 号：O641[理学—物理化学]