HIV-1整合酶与抑制剂金精三羧酸复合物的分子动力学模拟

用分子对接程序(Autodock)将含有一个Mg²⁺的HIV-1整合酶核心区(以下简称IN-A)与抑制剂小分子金精三羧酸(简称Aurin)进行对接,预测其未知的复合物结构,然后用分子动力学(MD)方法对IN-A与Aurin的对接结果进行了950 ps的模拟.MD模拟结果发现,IN-A与Aurin形成了两个稳定的氢键,Mg²⁺也与Aurin上的氧原子形成了稳定的配键,IN-A与Aurin之间的静电相互作用能和范德华相互作用能的平均值分别为-205.8和-162.7 kJ/mol.根据MD模拟得到的IN-A与Aurin相互作用后的构象变化信息,我们对对接复合物结构进行了修正,给出了更加合理和稳定的复合物预测结构.本工作得到的HIV-1整合酶与抑制剂Aurin的结合模式信息将有助于设计和改造出效果更好的抗HIV-1整合酶的先导化合物.

Molecular Dynamics Simulation on the Complex of HIV-1 Integrase and the Inhibitor Aurintricarboxylic Acid

Molecular dynamics simulation method was used to study the complex structure of HIV-1 integrase and its inhibitor aurintricarboxylic acid (Aurin). The HIV-1 integrase core domain (IN-A) with a Mg 2+ and inhibitor Aurin molecule are docked as a complex with the program Autodock. A 950 ps molecular dynamics simulation was carried out on the complex system. The simulation shows the stability of the complex. It was found that there are two stable hydrogen bonds between IN-A and Aurin in the predicted complex structure. The Mg 2+ is also chelated with an oxygen atom of Aurin. The mean electrostatic interaction and the mean van der Waals interaction between IN-A and Aurin are -205.8 and -162.7 kJ/mol, respectively. The result of our simulation and the predicted complex structure will be useful in designing anti HIV-1 integrase inhibitor.