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Mechanistic insights into the effects of key mutations on SARS-CoV-2 RBD-ACE2 binding

Aggarwal, A and Naskar, S and Maroli, N and Gorai, B and Dixit, NM and Maiti, PK (2021) Mechanistic insights into the effects of key mutations on SARS-CoV-2 RBD-ACE2 binding. In: Physical Chemistry Chemical Physics, 23 (46). pp. 26451-26458.

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Official URL: https://doi.org/10.1039/d1cp04005g


Some recent SARS-CoV-2 variants appear to have increased transmissibility compared to the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on the target cells and infect them. In this study, we provide atomic-level insights into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities for the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than for the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations. © the Owner Societies.

Item Type: Journal Article
Publication: Physical Chemistry Chemical Physics
Publisher: Royal Society of Chemistry
Additional Information: The copyright for this article belongs to the Author.
Keywords: Binding energy; Free energy; Molecular dynamics, Atomic levels; Binding affinities; Free-energy calculations; Hotspots; Mechanistics; Receptor-binding domains; Spike protein; Target cells; Wild types, SARS
Department/Centre: Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering
Division of Mechanical Sciences > Chemical Engineering
Division of Physical & Mathematical Sciences > Physics
Date Deposited: 06 Jan 2022 11:36
Last Modified: 06 Jan 2022 11:36
URI: http://eprints.iisc.ac.in/id/eprint/70810

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