新冠病毒蛋白酶与抗病毒药物分子相互作用的分子模拟研究

该工作通过研究抗病毒药物与新冠病毒Mpro的相互作用，理解药物分子对Mpro动力学的影响，对Mpro抑制剂的设计提供帮助.采用分子对接方法获得了Mpro与药物分子结合的复合物结构及其亲和力.常规的分子动力学模拟结果显示，测试的抗病毒药物均不能很好抑制Mpro结合位点处的动力学.通过副本交换的分子动力学模拟充分采样Mpro与不同药物分子结合的构象，分析不同药物分子对Mpro结合口袋形状及动力学产生的影响.结果显示不同药物分子通过与结合位点周围不同位置处氨基酸形成的不同的氢键网络，改变了Mpro结合口袋的形状.上述结果提示在未来的药物设计中，应充分考虑潜在抑制剂与Mpro结合口袋形成的氢键网络的重要性.

Molecular Simulation Study on the Interaction Between SARS-CoV-2 Main Protease and the Antiviral Inhibitors

In this study, we studied the interactions between the inhibitors and the main protease (Mpro) of SARS-CoV-2, to understand how the inhibitors influence the dynamics of Mpro of SARS-CoV-2. Firstly, we applied molecular docking to obtain the binding complex of the inhibitors and the main protease, and the binding affinities. The classical molecular dynamics simulations showed that all of the tested inhibitors cannot inhibit the dynamics of Mpro’s active pocket. The replica-exchange molecular dynamics simulations showed that the inhibitors influence the shape of the active pocket of Mpro. With the formation of hydrogen bonds between the inhibitor and different sites of the active pocket, the inhibitors affect the length and width of the pocket. Our study indicated that the drug design of Mpro should fully consider the importance of the hydrogen network between the potential inhibitor and the active pocket.