Predicting spike protein NTD mutations of SARS-CoV-2 causing immune evasion by molecular dynamics simulations
文献类型：期刊论文
| 作者 | Zhou, Liping1,2; Wu, Leyun1,2; Peng, Cheng1,2; Yang, Yanqing1,2; Shi, Yulong1,2; Gong, Likun2,3 ; Xu, Zhijian1,2; Zhu, Weiliang1,2
|
| 刊名 | PHYSICAL CHEMISTRY CHEMICAL PHYSICS
 |
| 出版日期 | 2022-02-02 |
| 卷号 | 24期号:5页码:3410-3419 |
| ISSN号 | 1463-9076 |
| DOI | 10.1039/d1cp05059a |
| 通讯作者 | Xu, Zhijian(zjxu@simm.ac.cn) ; Zhu, Weiliang(wlzhu@simm.ac.cn) |
| 英文摘要 | The coronavirus disease 2019 (COVID-19) pandemic was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Among all the potential targets studied for developing drugs and antibodies, the spike (S) protein is the most striking one, which is on the surface of the virus. In contrast with the intensively investigated immunodominant receptor-binding domain (RBD) of the protein, little is known about the neutralizing antibody binding mechanisms of the N-terminal domain (NTD), let alone the effects of NTD mutations on antibody binding and thereby the risk of immune evasion. Based on 400 ns molecular dynamics simulation for 11 NTD-antibody complexes together with other computational approaches in this study, we investigated critical residues for NTD-antibody binding and their detailed mechanisms. The results show that 36 residues on the NTD including R246, Y144, K147, Y248, L249 and P251 are critically involved in the direct interaction of the NTD with many monoclonal antibodies (mAbs), indicating that the viruses harboring these residue mutations may have a high risk of immune evasion. Binding free energy calculations and an interaction mechanism study reveal that R246I, which is present in the Beta (B.1.351/501Y.V2) variant, may have various impacts on current NTD antibodies through abolishing the hydrogen bonds and electrostatic interaction with the antibodies or affecting other interface residues. Therefore, special attention should be paid to the mutations of these key residues in future antibody and vaccine design and development. |
| WOS关键词 | GLYCAN READER ; BINDING ; ACE2 ; RBD |
| 资助项目 | Natural Science Foundation of Shanghai[21ZR1475600] ; National Key Research and Development Program of China[2016YFA0502301] ; National Key Research and Development Program of China[2017YFB0202601] |
| WOS研究方向 | Chemistry ; Physics |
| 语种 | 英语 |
| 出版者 | ROYAL SOC CHEMISTRY |
| WOS记录号 | WOS:000746110900001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/300574]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Xu, Zhijian; Zhu, Weiliang |
| 作者单位 | 1.Chinese Acad Sci, Drug Discovery & Design Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Univ Chinese Acad Sci, Sch Pharm, 19A Yuquan Rd, Beijing 100049, Peoples R China 3.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Liping,Wu, Leyun,Peng, Cheng,et al. Predicting spike protein NTD mutations of SARS-CoV-2 causing immune evasion by molecular dynamics simulations[J]. PHYSICAL CHEMISTRY CHEMICAL PHYSICS,2022,24(5):3410-3419. |
| APA | Zhou, Liping.,Wu, Leyun.,Peng, Cheng.,Yang, Yanqing.,Shi, Yulong.,...&Zhu, Weiliang.(2022).Predicting spike protein NTD mutations of SARS-CoV-2 causing immune evasion by molecular dynamics simulations.PHYSICAL CHEMISTRY CHEMICAL PHYSICS,24(5),3410-3419. |
| MLA | Zhou, Liping,et al."Predicting spike protein NTD mutations of SARS-CoV-2 causing immune evasion by molecular dynamics simulations".PHYSICAL CHEMISTRY CHEMICAL PHYSICS 24.5(2022):3410-3419. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。