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. 2022 Jul:146:105633.
doi: 10.1016/j.compbiomed.2022.105633. Epub 2022 May 17.

Omicron variant receptor-binding domain phylogenetics and molecular dynamics

Mahmoud Kandeel  1 , Wael El-Deeb  2
Affiliations
Free PMC article

Omicron variant receptor-binding domain phylogenetics and molecular dynamics

Mahmoud Kandeel et al. Comput Biol Med. 2022 Jul.
Free PMC article

Abstract

Background: We investigated the evolutionary relationships, mutations, antigenic epitopes, and structural dynamics of the receptor-binding domain (RBD) of SARS-CoV-2, Omicron and other recently evolved variants.

Methods: The RBD of SARS-CoV-2 and its Omicron, Alpha, Beta, Gamma, Delta, and Mu variants were subjected to pairwise sequence matrix evaluation, antigenic epitope prediction, and phylogenetic relationship and structural dynamics analyses.

Results: The Omicron RBD contained 13-15 amino acid mutations, of which 12 were new and three conserved with other variants. In addition, two mutations found in the Alpha, Beta, Gamma, and Mu variants were not found in the Omicron RBD. The ultrametric clustering unweighted pair group method with arithmetic mean identified Omicron as a novel monophyletic class, but the neighbor-joining method clustered Omicron with Alpha and Delta variants. In the SARS-CoV-2 RBD, five main antigenic epitopes were predicted, and these epitopes were conserved across all SARS-CoV-2 variants tested. Surprisingly, the additional mutations in the Omicron variant increased the size of the expected antigenic sites in two of these antigenic epitopes. Molecular dynamics (MD) simulations revealed higher root-mean-square deviation in the Omicron RBD, greater residue fluctuation at residues 32-42 and 140-160, and increased solvent-accessible surface area.

Conclusions: The Omicron RBD mutations indicate the variant is within a new phylogenetic class of SARS-CoV-2 and significantly impact RBD structure, conformation, and molecular dynamics. However, conserved anticipated antigenic sites may imply partial changes in receptor affinity and response to immune reactions. Omicron RBD binding with the angiotensin-converting enzyme 2 receptor was suggested to be weaker than the original SARS-CoV-2 binding in MD simulations.

Keywords: COVID-19; Omicron variant; Phylogenetics; SARS-CoV-2.

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Figures

Fig. 1
Fig. 1
Multiple sequence alignment of RBD from SARS-CoV-2 and its Omicron, Alpha, Beta, Gamma, Delta, and Mu variants. The mutated residues are highlighted in red.
Fig. 2
Fig. 2
Pairwise comparative matrix of Omicron and SARS-CoV-2 variants. A) The upper diagonal panel shows the differences in amino acid content. The lower diagonal panel depicts percent identity. B) The upper diagonal panel shows the gaps in the sequence alignment. The lower diagonal panel provides the residues' identities.
Fig. 3
Fig. 3
Comparison of different methods of analyzing phylogenetic trees constructed based on RBD analysis results: A) the NJ method and JTT substitution model, B) the NJ method and WAG substitution model, C) the UPGMA method and JTT substitution model, and D) the UPGMA method and WAG substitution model.
Fig. 4
Fig. 4
Amino acid sequence alignment of Omicron and SARS-CoV-2 RBD. The top five predicted antigenic epitope sites are highlighted.
Fig. 5
Fig. 5
The sites of antigenic epitopes in SARS-CoV-2 and Omicron RBD. The sites are numbered 1–5 according to their EMBOSS antigenic analysis score.
Fig. 6
Fig. 6
The RMSD of SARS-CoV-2 and Omicron RBD during the 100-ns MD simulation. A) SARS-CoV-2 and Omicron RBD RMSD implemented by GROMACS software analysis. B) SARS-CoV-2 and Omicron RBD RMSD values implemented by Desmond software analysis.
Fig. 7
Fig. 7
The RMSF of SARS-CoV-2 and Omicron RBDs during the 100-ns MD simulation. A) SARS-CoV-2 and Omicron RBD RMSF values implemented by GROMACS software analysis. B) SARS-CoV-2 and Omicron RBD RMSF values implemented by Desmond software analysis.
Fig. 8
Fig. 8
The genetic correlation (Rg) of SARS-CoV-2 and Omicron RBD during the 100-ns MD simulation. A) SARS-CoV-2 and Omicron RBD Rg values implemented by GROMACS software analysis. B) SARS-CoV-2 and Omicron RBD Rg values implemented by Desmond software analysis.
Fig. 9
Fig. 9
The solvent-accessible surface areas (SASAs) of SARS-CoV-2 and Omicron RBDs during the 100-ns MD simulation. A) SARS-CoV-2 and Omicron RBD SASAs implemented by GROMACS software analysis. B) SARS-CoV-2 and omicron RBD SASAs implemented by Desmond software analysis.
Fig. 10
Fig. 10
The hydrogen bonds of SARS-CoV-2 and Omicron RBDs during the 100-ns MD simulation calculated by GROMACS software.
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