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

吴徐伟; 李星宇; 李华; 李振海; 陈伟; 李德昌

doi:10.21656/1000-0887.420280

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

doi: 10.21656/1000-0887.420280

1. 浙江大学应用力学研究所, 杭州 310012;
2. 上海大学力学与工程科学学院, 上海 200444;
3. 浙江大学医学部基础医学院, 杭州 310012

详细信息

作者简介:
吴徐伟（1997—），男，硕士生（E-mail: 21924076@zju.edu.cn）;李振海（1983—），男，副教授，博士（通讯作者. E-mail: lizhshu@shu.edu.cn）;李德昌（1984—），男，副教授，博士（通讯作者. E-mail: dcli@zju.edu.cn）.

通讯作者:
李振海（1983—），男，副教授，博士（通讯作者. E-mail: lizhshu@shu.edu.cn）

中图分类号: O39|R392
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出版历程
- 收稿日期: 2021-09-13
- 修回日期: 2021-09-27

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

1. Institute of Applied Mechanics, Zhejiang University, Hangzhou 310012, P.R.China;
2. School of Mechanics and Engineering Science, Shanghai University, Shanghai 200444, P.R.China;
3. School of Basic Medical Sciences, School of Medicine, Zhejiang University, Hangzhou 310012, P.R.China

摘要

摘要: 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.
- 新冠病毒蛋白酶 /
- 抗病毒药物分子 /
- 分子对接 /
- 分子动力学
Abstract: 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.
- SARS-CoV-2 main protease /
- antiviral inhibitors /
- molecular docking /
- molecular dynamics simulation

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参考文献(28)

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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

doi: 10.21656/1000-0887.420280

作者简介:
吴徐伟（1997—），男，硕士生（E-mail: 21924076@zju.edu.cn）;李振海（1983—），男，副教授，博士（通讯作者. E-mail: lizhshu@shu.edu.cn）;李德昌（1984—），男，副教授，博士（通讯作者. E-mail: dcli@zju.edu.cn）.

通讯作者:
李振海（1983—），男，副教授，博士（通讯作者. E-mail: lizhshu@shu.edu.cn）

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

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留言板

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

doi: 10.21656/1000-0887.420280

作者简介: 吴徐伟（1997—），男，硕士生（E-mail: 21924076@zju.edu.cn）;李振海（1983—），男，副教授，博士（通讯作者. E-mail: lizhshu@shu.edu.cn）;李德昌（1984—），男，副教授，博士（通讯作者. E-mail: dcli@zju.edu.cn）.

通讯作者: 李振海（1983—），男，副教授，博士（通讯作者. E-mail: lizhshu@shu.edu.cn）

计量

出版历程

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

计量

出版历程

目录

作者简介:
吴徐伟（1997—），男，硕士生（E-mail: 21924076@zju.edu.cn）;李振海（1983—），男，副教授，博士（通讯作者. E-mail: lizhshu@shu.edu.cn）;李德昌（1984—），男，副教授，博士（通讯作者. E-mail: dcli@zju.edu.cn）.

通讯作者:
李振海（1983—），男，副教授，博士（通讯作者. E-mail: lizhshu@shu.edu.cn）