二芳基三嗪类HIV-1逆转录酶抑制剂的分子对接及3D-QSAR研究

Molecular Docking and 3D-QSAR Research of Diaryltriazines Derivatives as HIV-1 Reverse Transcriptase Inhibitors

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。

The molecular docking followed by comparative molecular similarity index analysis（CoMSIA） was employed to the three-dimensional quantitative structure-activity relationship（3D-QSAR） studies of HIV-1 reverse transcriptase inhibitory activities of 40 diaryltriazines derivatives.The results showed that hydrophobic interactions between the bottom of binding pocket and two aromatic rings of ligands,electrostatic interactions between the binding pocket and the triazine ring and R4 substituent,and steric hindrance between the binding site and the R4 substituent were the dominant factors affecting the binding affinities.Based on the docking conformations,CoMSIA were employed to the QSAR studies of this dataset.The number of principal components,r2,q2（leave-one-out,LOO）,r2pred of the optimal CoMSIA model were 6,0.971,0.738,and 0.833 respectively.The conclusions obtained from contour map analysis were in agreement with the docking results.