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对40个二芳基三嗪类HIV-1逆转录酶抑制剂进行了分子对接研究,结果表明,2个疏水性芳香取代基团与结合口袋底部形成的疏水和范德华相互作用、三嗪环母核及其R4取代基与结合位点产生的氢键和静电作用以及R4取代基与袋口形成的空间位阻效应是影响该系列化合物活性的重要因素。根据对接优势构象进行分子叠合和比较分子相似性指数分析(CoMSIA)研究,建立了4个高预测能力的3-D构效关系模型,其中以选用立体场、静电场和疏水场建立的CoMSIA模型为最优,其主成分,r2,q2(LOO)和r2pred分别为6,0.971、0.738和0.833。模型结果表明,3个力场对活性贡献由大到小依次为疏水场、静电场和立体场。CoMSIA等势图分析结果与对接分析相一致。
A molecular docking study of 40 diaryltriazine HIV-1 reverse transcriptase inhibitors showed that two hydrophobic aromatic substituents interact with the hydrophobic and van der Waals formed at the bottom of the binding pocket. The triazine ring parent The hydrogen bonding and electrostatic interactions between the nucleus and its R4 substituents and the binding sites and the steric hindrance effect of R4 substituents and pocket formation are important factors that influence the activity of the compounds. According to the study of molecular overlap and comparative molecular similarity index analysis (CoMSIA), four 3-D structure-activity relationship models with high predictive ability were established. Among them, CoMSIA, which was established by choosing three-dimensional field, electrostatic field and hydrophobic field, The model is optimal with the main components r2, q2 (LOO) and r2pred of 6, 0.971, 0.738 and 0.833, respectively. The model results show that the contribution of the three force fields to hydrophobicity, electrostatic field and stereo field are in turn order of magnitude. CoMSIA equipotential graph analysis results are consistent with the docking analysis.