【摘要】 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.更多还原

【Abstract】 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 targeting HIV- 1 protease.更多还原