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Exploring the Binding Affinity and Mechanism between ACE2 and the Trimers of Delta and Omicron Spike Proteins by Molecular Dynamics Simulation and Bioassay

文献类型：期刊论文

作者Zhou, Liping6,7; Liu, Tingting5,6; Mo, Mengxia4; Shi, Yulong6,7; Wu, Leyun6,7; Li, Yishui3; Qin, Qiuping5,6; Zhu, Weiliang2,6,7; Wu, Chengkun3; Gong, Likun6
刊名JOURNAL OF CHEMICAL INFORMATION AND MODELING
出版日期2022-09-02
页码11
ISSN号1549-9596
DOI10.1021/acs.jcim.2c00881
通讯作者Zhu, Weiliang(wlzhu@simm.ac.cn) ; Wu, Chengkun(chengkun_wu@nudt.edu.cn) ; Gong, Likun(lkgong@cdser.simm.ac.cn) ; Xu, Zhijian(zjxu@simm.ac.cn)
英文摘要Five major variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged and posed challenges in controlling the pandemic. Among them, the current dominant variant, viz., Omicron, has raised serious concerns about its infectiousness and antibody neutralization. However, few studies pay attention to the effect of the mutations on the dynamic interaction network of Omicron S protein trimers binding to the host angiotensin-converting enzyme 2 (ACE2). In this study, we conducted molecular dynamics (MD) simulations and enzyme linked immunosorbent assay (ELISA) to explore the binding strength and mechanism of wild type (WT), Delta, and Omicron S protein trimers to ACE2. The results showed that the binding capacities of both the two variants' S protein trimers to ACE2 are enhanced in varying degrees, indicating possibly higher cell infectiousness. Energy decomposition and protein-protein interaction network analysis suggested that both the mutational and conserved sites make effects on the increase in the overall affinity through a variety of interactions. The experimentally determined KD values by biolayer interferometry (BLI) and the predicted binding free energies of the RBDs of Delta and Omicron to mAb HLX70 revealed that the two variants may have the high risk of immune evasion from the mAb. These results are not only helpful in understanding the binding strength and mechanism of S protein trimer-ACE2 but also beneficial for drug, especially for antibody development.
WOS关键词FORCE-FIELD
资助项目Key project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources ; National Key R&D Program of China[2060302] ; Natural Science Foundation of Shanghai[2016YFA0502301] ; [21ZR1475600] ; [22S11902100]
WOS研究方向Pharmacology & Pharmacy ; Chemistry ; Computer Science
语种英语
WOS记录号WOS:000852032100001
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/302410]  
专题新药研究国家重点实验室
通讯作者Zhu, Weiliang; Wu, Chengkun; Gong, Likun; Xu, Zhijian
作者单位1.State Key Lab Dao Di Herbs, Beijing 100700, Peoples R China
2.Pilot Natl Lab Marine Sci & Technol Qingdao, Open Studio Druggabil Res Marine Nat Prod, Qingdao 266237, Peoples R China
3.Natl Univ Def Technol, Inst Quantum Informat, Coll Comp Sci & Technol, State Key Lab High Performance Comp, Changsha 410073, Peoples R China
4.Hunan Univ, Coll Comp Sci & Elect Engn, Changsha 410082, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, Sch Pharm, Shanghai 201203, Peoples R China
6.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
7.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhou, Liping,Liu, Tingting,Mo, Mengxia,et al. Exploring the Binding Affinity and Mechanism between ACE2 and the Trimers of Delta and Omicron Spike Proteins by Molecular Dynamics Simulation and Bioassay[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2022:11.
APA Zhou, Liping.,Liu, Tingting.,Mo, Mengxia.,Shi, Yulong.,Wu, Leyun.,...&Xu, Zhijian.(2022).Exploring the Binding Affinity and Mechanism between ACE2 and the Trimers of Delta and Omicron Spike Proteins by Molecular Dynamics Simulation and Bioassay.JOURNAL OF CHEMICAL INFORMATION AND MODELING,11.
MLA Zhou, Liping,et al."Exploring the Binding Affinity and Mechanism between ACE2 and the Trimers of Delta and Omicron Spike Proteins by Molecular Dynamics Simulation and Bioassay".JOURNAL OF CHEMICAL INFORMATION AND MODELING (2022):11.

入库方式： OAI收割

来源：上海药物研究所

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