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.
|Original language||American English|
|Number of pages||8|
|Journal||Computational and Structural Biotechnology Journal|
|State||Published - Jan 2021|
Bibliographical noteFunding Information:
Research reported in this publication was supported by the SJTU Global Strategic Partnership Fund (2020 SJTU-HUJI), the National Natural Science Foundation of China (Nos. 21901157 and 81901069) and the National Key R&D Program of China (2021YFC2100100).
© 2021 The Authors
- Binding affinity
- Coronavirus variant
- Residue mutation
- Spike glycoprotein