分子动力学研究抑制剂APV与HIV-1蛋白酶的作用机制

摘要

Molecular dynamics simulation and binding free energy calculation was performed to study the binding mode of inhibitor APV to HIV-1 protease. The results show that van der walls energy is the main force driving the binding of APV to HIV-1 protease. Residue-based free energy decomposition was adopted to calculate the inhibitor-residue interaction and the results suggest that nine residues Gly27 , Ile32 , Val47 , Ile50 , Ile84 , Ala28′, Gly49′, Ile50′and Arg87′in HIV-1 protease produce strong interactions with APV, at the same time, these results also show that the CH-π, CH-O and polar interaction are the main ones between APV and HIV-1 protease. We expect that this study can provide significant contributions to the designs of anti-AIDS targe-ting HIV-1 protease.%采用分子动力学模拟和结合自由能计算研究了抑制剂APV与HIV-1蛋白酶的作用机制．研究结果表明范德瓦尔斯作用主控了APV与HIV-1蛋白酶的结合．采用基于残基的自由能分解方法计算了抑制剂-残基相互作用,结果表明9个残基Gly27、Ile32、Val47、Ile50、Ile84、Ala28′、Gly49′、Ile50′和Arg87′与APV产生了大于1．0 kcal/mol的强相互作用,而且证明CH-π,CH-O相互作用和极性作用是其结合的主要形式．期待该结果可以为以HIV-1蛋白酶为靶标的抗艾滋病药物设计提供理论上的指导．