分子动力学研究抑制剂APV与HIV-1蛋白酶的作用机制  

Molecular dynamics insights into binding mode of inhibitor APV to HIV-1 protease

作　　者：时术华[1] 张少龙[2] 张庆刚[2] 

机构地区：[1]山东建筑大学理学院,济南250101 [2]山东师范大学物理与电子科学学院,济南250014

出　　处：《原子与分子物理学报》2015年第5期885-890,共6页Journal of Atomic and Molecular Physics

基　　金：国家自然科学基金(11274206);山东省自然科学基金(ZR2011HM048;ZR2013AM014);山东建筑大学博士启动基金(XNBS1268)

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.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, Va147, 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.

关 键 词：分子动力学 结合自由能 HIV-1蛋白酶 MM-PBSA 

分 类 号：Q641.12[生物学—生物物理学]