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Molecular dynamics of spike variants in the locked conformation: RBD interfaces, fatty acid binding and furin cleavage sites

View ORCID ProfileDeborah K. Shoemark, View ORCID ProfileA. Sofia F. Oliveira, Andrew D. Davidson, View ORCID ProfileImre Berger, View ORCID ProfileChristiane Schaffitzel, View ORCID ProfileAdrian J. Mulholland
doi: https://doi.org/10.1101/2022.05.06.490927
Deborah K. Shoemark
aSchool of Biochemistry, University of Bristol, Bristol BS8 1TD, UK
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  • For correspondence: adrian.mulholland@bristol.ac.uk deb.shoemark@bristol.ac.uk
A. Sofia F. Oliveira
aSchool of Biochemistry, University of Bristol, Bristol BS8 1TD, UK
bCentre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK
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Andrew D. Davidson
cSchool of Cellular and Molecular Medicine, University of Bristol, University Walk, Bristol, BS8 1TD, UK
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Imre Berger
aSchool of Biochemistry, University of Bristol, Bristol BS8 1TD, UK
dMax Planck Bristol Centre for Minimal Biology, Cantock’s Close, Bristol BS8 1TS, UK
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Christiane Schaffitzel
aSchool of Biochemistry, University of Bristol, Bristol BS8 1TD, UK
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Adrian J. Mulholland
bCentre for Computational Chemistry, School of Chemistry, University of Bristol, Bristol BS8 1TS, UK
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  • For correspondence: adrian.mulholland@bristol.ac.uk deb.shoemark@bristol.ac.uk
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Abstract

Since December 2019 the SARS-CoV-2 virus has infected billions of people around the world and caused millions of deaths. The ability for this RNA virus to mutate has produced variants that have been responsible for waves of infections across the globe. The spike protein on the surface of the SARS-CoV-2 virion is responsible for cell entry in the infection process. Here we have studied the spike proteins from the Original, Alpha (B.1.1.7), Delta (B1.617.2), Delta-plus (B1.617.2-AY1), Omicron BA.1 and Omicron BA.2 variants. Using models built from cryo-EM structures with linoleate bound (6BZ5.pdb) and the N-terminal domain from 7JJI.pdb, each is built from the first residue, with missing loops modelled and 45 disulphides per trimer. Each spike variant was modified from the same Original model framework to maximise comparability. Three replicate, 200 ns atomistic molecular dynamics simulations were performed for each case. (These data also provide the basis for further, non-equilibrium molecular dynamics simulations, published elsewhere.) The analysis of our equilibrium molecular dynamics reveals that sequence variation at the closed receptor binding domain interface particularly for Omicron BA.2 has implications for the avidity of the locked conformation, with potential effects on Omicron BA.1 and Delta-plus. Linoleate binding has a mildly stabilizing effect on furin cleavage site motions in the Original and Alpha variants, but has no effect in Delta, Delta-plus and slightly increases motions at this site for Omicron BA.1, but not BA.2, under these simulation conditions.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted May 08, 2022.
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Molecular dynamics of spike variants in the locked conformation: RBD interfaces, fatty acid binding and furin cleavage sites
Deborah K. Shoemark, A. Sofia F. Oliveira, Andrew D. Davidson, Imre Berger, Christiane Schaffitzel, Adrian J. Mulholland
bioRxiv 2022.05.06.490927; doi: https://doi.org/10.1101/2022.05.06.490927
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Molecular dynamics of spike variants in the locked conformation: RBD interfaces, fatty acid binding and furin cleavage sites
Deborah K. Shoemark, A. Sofia F. Oliveira, Andrew D. Davidson, Imre Berger, Christiane Schaffitzel, Adrian J. Mulholland
bioRxiv 2022.05.06.490927; doi: https://doi.org/10.1101/2022.05.06.490927

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