CAJ | 학술논문

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、Glu152的作用力越大，药物活性越高， Lys 159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 HI V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。
목적：결합조조집(RS)이론화비교잔기상호작용(CoRIA)연구HIV정합매억제제적구효관계(SAR)；방법：선택일계렬영향억제제여IN단백결합적관건잔기，채용기여억제제적비건작용력수거(전자작용력화범덕화작용력)，이용RS이론건립료결책규칙，분석료상응적구효관계。결과：총체표명화합물여Asp64、Thr66、Asp116、Glu152적작용력월대，약물활성월고， Lys 159적작용정호상반。동시불동작용력지간존재길항작용，위반상술규률，영향억제제적활성。결론：본문적결과대연구항 HI V약물적약리、작용궤제급정합매억제제적개발균유일정적의의。
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.