TY - JOUR
T1 - Binding affinity and mechanisms of SARS-CoV-2 variants
AU - Han, Yanqiang
AU - Wang, Zhilong
AU - Wei, Zhiyun
AU - Schapiro, Igor
AU - Li, Jinjin
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/1
Y1 - 2021/1
N2 - During the rapid worldwide spread of SARS-CoV-2, the viral genome has been undergoing numerous mutations, especially in the spike (S) glycoprotein gene that encode a type-I fusion protein, which plays an important role in the infectivity and transmissibility of the virus into the host cell. In this work, we studied the effect of S glycoprotein residue mutations on the binding affinity and mechanisms of SARS-CoV-2 using molecular dynamics simulations and sequence analysis. We quantitatively determined the degrees of binding affinity caused by different S glycoprotein mutations, and the result indicated that the 501Y.V1 variant yielded the highest enhancements in binding affinity (increased by 36.8%), followed by the N439K variant (increased by 29.5%) and the 501Y.V2 variant (increased by 19.6%). We further studied the structures, chemical bonds, binding free energies (enthalpy and entropy), and residue contribution decompositions of these variants to provide physical explanations for the changes in SARS-CoV-2 binding affinity caused by these residue mutations. This research identified the binding affinity differences of the SARS-CoV-2 variants and provides a basis for further surveillance, diagnosis, and evaluation of mutated viruses.
AB - During the rapid worldwide spread of SARS-CoV-2, the viral genome has been undergoing numerous mutations, especially in the spike (S) glycoprotein gene that encode a type-I fusion protein, which plays an important role in the infectivity and transmissibility of the virus into the host cell. In this work, we studied the effect of S glycoprotein residue mutations on the binding affinity and mechanisms of SARS-CoV-2 using molecular dynamics simulations and sequence analysis. We quantitatively determined the degrees of binding affinity caused by different S glycoprotein mutations, and the result indicated that the 501Y.V1 variant yielded the highest enhancements in binding affinity (increased by 36.8%), followed by the N439K variant (increased by 29.5%) and the 501Y.V2 variant (increased by 19.6%). We further studied the structures, chemical bonds, binding free energies (enthalpy and entropy), and residue contribution decompositions of these variants to provide physical explanations for the changes in SARS-CoV-2 binding affinity caused by these residue mutations. This research identified the binding affinity differences of the SARS-CoV-2 variants and provides a basis for further surveillance, diagnosis, and evaluation of mutated viruses.
KW - Binding affinity
KW - Coronavirus variant
KW - Residue mutation
KW - SARS‐CoV‐2
KW - Spike glycoprotein
UR - http://www.scopus.com/inward/record.url?scp=85111766326&partnerID=8YFLogxK
U2 - 10.1016/j.csbj.2021.07.026
DO - 10.1016/j.csbj.2021.07.026
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AN - SCOPUS:85111766326
SN - 2001-0370
VL - 19
SP - 4184
EP - 4191
JO - Computational and Structural Biotechnology Journal
JF - Computational and Structural Biotechnology Journal
ER -