粗糙集-比较残基相互作用分析法研究HIV整合酶抑制剂的构效关系

The application of rough sets in SAR analysis of HIV integrase inhibitors

目的;结合粗糙集(RS)理论和比较残基相互作用(CoRIA)研究HⅣ整合酶抑制剂的构效关系(SAR);方法:选择一系列影响抑制剂与IN蛋白结合的关键残基,采用其与抑制剂的非键作用力数据(电子作用力和范德华作用力),利用RS理论建立了决策规则,分析了相应的构效关系。结果:总体表明化合物与Asp64、Thr66、Asp116、G1u152的作用力越大,药物活性越高,Lys159的作用正好相反。同时不同作用力之间存在拮抗作用,违反上述规律,影响抑制剂的活性。结论:本文的结果对研究抗HIv药物的药理、作用机制及整合酶抑制剂的开发均有一定的意义。

The structure-activity relationship study of HIV integrase inhibitors （INs） was performed with RS （rough sets） method and comparative residue interaction analysis（CoRIA）. Several crucial residue that impact the combination with INs were selected, non-bonded interaction energies（van der Waals and Coulombic） of the inhibitors with these residues were studied by RS method, and decision rules were analyzed. The RS analysis suggest that the greater interaction energies of Asp64, Thr66, Asp116, Glu152 with INs comes greater activity, while Lys159 is just the opposite. And different interaction energies have antagonism which against above conclusion. The result obtained in this study is instructive to the study of pharmacodynamics, mechanism of INs and development of INs＇ derivatives.