HIV-1逆转录酶抑制剂的3D-QSAR和分子对接研究

Study on 3D-QSAR and molecular docking of HIV-1 reverse transcriptase inhibitors

采用分子对接和三维定量构效关系研究了二芳基苯胺衍生物与HIV-1非核苷类逆转录酶的相互作用,并运用经典的三维全息原子场作用矢量的方法(3D-HoVAIF)和多元线性回归方法(MLR)研究了药物分子的化学结构与生物活性之间的关系.MLR建模得出的复相关系数(R_(cum))为0.949、留一法交互校验复相关系数(QCV)为0.799,从该结果可以看出,三维定量构效关系对化合物的抗艾滋病活性具有比较好的预测能力.最后,运用分子对接研究了小分子药物和大分子HIV-1逆转录酶的氨基酸活性残基之间的结合模式,对今后设计合成新的抗艾滋病药物具有很好的指导作用.

In this study,using molecular docking and three-dimensional quantitative structureactivity relationship as a method to study the interaction between a series of diaryl aniline analogues and HIV-1non nucleoside reverse transcriptase,through the establishment of threedimensional quantitative structure-activity relationship model and multiple linear regression（MLR）model study the relationship between structure and biological activity of the drug moleculesl.The correlation coefficient（R（cum））of MLR is 0.949,the correlation coefficient（QCV）is 0.799,the results show that the three-dimensional quantitative structure-activity relationship has good prediction ability for the anti HIV activity of the compound.The binding model of small molecule drugs and macromolecular HIV-1 reverse transcriptase active amino acid residues was studied by molecular docking.It is a good guide for the design and synthesis of new anti AIDS drugs.