Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations

doi:10.3389/fimmu.2021.730099

	Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations
	Buratto, Damiano1 ; Saxena, Abhishek1 ; Ji, Qun1 ; Yang, Guang1 ; Pantano, Sergio1,2 ; Zonta, Francesco1
	2021-11-11
发表期刊	FRONTIERS IN IMMUNOLOGY
ISSN	1664-3224
卷号	12
DOI	10.3389/fimmu.2021.730099
摘要	SARS-CoV-2 infects humans and causes Coronavirus disease 2019 (COVID-19). The S1 domain of the spike glycoprotein of SARS-CoV-2 binds to human angiotensin-converting enzyme 2 (hACE2) via its receptor-binding domain, while the S2 domain facilitates fusion between the virus and the host cell membrane for entry. The spike glycoprotein of circulating SARS-CoV-2 genomes is a mutation hotspot. Some mutations may affect the binding affinity for hACE2, while others may modulate S-glycoprotein expression, or they could result in a virus that can escape from antibodies generated by infection with the original variant or by vaccination. Since a large number of variants are emerging, it is of vital importance to be able to rapidly assess their characteristics: while changes of binding affinity alone do not always cause direct advantages for the virus, they still can provide important insights on where the evolutionary pressure is directed. Here, we propose a simple and cost-effective computational protocol based on Molecular Dynamics simulations to rapidly screen the ability of mutated spike protein to bind to the hACE2 receptor and selected neutralizing biomolecules. Our results show that it is possible to achieve rapid and reliable predictions of binding affinities. A similar approach can be used to perform preliminary screenings of the potential effects of S-RBD mutations, helping to prioritize the more time-consuming and expensive experimental work.
关键词	COVID-19 SARS-CoV-2 Spike-RBD human ACE2 binding affinity neutralizing antibodies protein-protein interaction molecular dynamics
URL	查看原文
收录类别	SCIE
语种	英语
WOS研究方向	Immunology
WOS类目	Immunology
WOS记录号	WOS:000725567200001
出版者	FRONTIERS MEDIA SA
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/134170
专题	免疫化学研究所_特聘教授组_Michael Levitt组免疫化学研究所免疫化学研究所_特聘教授组_功能筛选实验室免疫化学研究所_特聘教授组_抗体设计学实验室
通讯作者	Zonta, Francesco
作者单位	1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China; 2.Inst Pasteur Montevideo, Montevideo, Uruguay
第一作者单位	免疫化学研究所
通讯作者单位	免疫化学研究所
第一作者的第一单位	免疫化学研究所
推荐引用方式 GB/T 7714	Buratto, Damiano,Saxena, Abhishek,Ji, Qun,et al. Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations[J]. FRONTIERS IN IMMUNOLOGY,2021,12.
APA	Buratto, Damiano,Saxena, Abhishek,Ji, Qun,Yang, Guang,Pantano, Sergio,&Zonta, Francesco.(2021).Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations.FRONTIERS IN IMMUNOLOGY,12.
MLA	Buratto, Damiano,et al."Rapid Assessment of Binding Affinity of SARS-COV-2 Spike Protein to the Human Angiotensin-Converting Enzyme 2 Receptor and to Neutralizing Biomolecules Based on Computer Simulations".FRONTIERS IN IMMUNOLOGY 12(2021).