HIV-1蛋白酶与抑制剂结合中桥接水分子作用的QM/MM研究

Hybrid QM/MM Study on Interfacial Water Molecular Effects in the Binding of HIV-1 Protease and Inhibitors

对HIV-1蛋白酶与抑制剂2AH和4AH结合的两个复合物体系进行了水溶液环境下量子力学分子力学混合方法(hybrid QM/MM)的1ns分子动力学模拟,用MM-GBSA方法得到桥接水分子W301与HIV-1蛋白酶和抑制剂结合体的结合自由能分别为-24.93 kJ/mol和-20.29 kJ/mol,表明W301在抑制剂和HIV-1蛋白酶结合的过程中起到了不能被忽略的作用。

We performed l ns molecular dynamics simulations of hybrid quantum mechanics/ molecular mechanics （QM/MM） for two compounds that were formed by the binding of HIV-1 protease and inhibitor 2AH and 4AH in water solution. The binding free energy of interfacial water molecule W301 and the compounds of HIV-1 protease and inhibitors 2AH and 4AH by MM-GBSA were - 24.93 kJ/mol and - 20.29 kJ/mol. It demonstrated that W301 played an important role in the binding of HIV-1 protease and inhibitor , so it was not neglectable.