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. 2022 May 23;11(5):797.
doi: 10.3390/biology11050797.

An Insight Based on Computational Analysis of the Interaction between the Receptor-Binding Domain of the Omicron Variants and Human Angiotensin-Converting Enzyme 2

Ismail Celik  1 , Magda H Abdellattif  2 , Trina Ekawati Tallei  3
Affiliations

An Insight Based on Computational Analysis of the Interaction between the Receptor-Binding Domain of the Omicron Variants and Human Angiotensin-Converting Enzyme 2

Ismail Celik et al. Biology (Basel). .

Abstract

Concerns have been raised about the high number of mutations in the spike protein of the new emergence of the highly transmissible Omicron variant (B.1.1529 lineage) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This variant's extraordinary ability to evade antibodies would significantly impair the current vaccination program. This present study aimed to computationally analyze the interaction between the receptor-binding domain (RBD) in the spike protein of Omicron variants and human angiotensin-converting enzyme 2 (hACE2). The docking results indicated that Omicron BA.2 has exceptionally strong interactions with hACE2 in comparison to Omicron BA.1, Delta, and wild-type, as indicated by various parameters such as salt bridge, hydrogen bond, and non-bonded interactions. The results of the molecular dynamics simulation study corroborate these findings, indicating that Omicron BA.2 has a strong and stable interaction with hACE2. This study provides insight into the development of an effective intervention against this variant.

Keywords: Omicron; binding mechanism; computational analysis; receptor-binding domain; spike protein.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The phylogeny of Omicron and Delta variant based on mutation on their Spike protein (https://nextstrain.org/ncov/gisaid/global?c=S1_mutations&dmin=2021-12-13; accessed on 11 February 2022).
Figure 2
Figure 2
Multiple sequence alignment of the receptor-binding domain of SARS-CoV-2 Delta and Omicron variants.
Figure 3
Figure 3
(A) Ramachandran plot; (B) Z-score; and (C) residue scores plot for RBD of Omicron BA.2 variant.
Figure 4
Figure 4
(A) The 3D visualization of Omicron BA.2-ACE2 complex interaction (ACE2 is denoted in green, whereas BA.2 RBD is denoted in blue); (B) interface of Omicron BA.2-ACE2 complex interaction. Residue colors: positively charged (blue): His, Lys, Arg; negatively-charged (red): Asp, Glu; neutral (green): Ser, Thr, Asn, Gln; aliphatic (gray): Ala, Val, Leu, Ile, Met; aromatic (purple): Phe, Tyr, Trp; Pro; and Gly (orange).
Figure 5
Figure 5
(A) The 3D visualization of Omicron BA.1-ACE2 complex interaction (ACE2 is denoted in green, whereas BA.1 RBD is denoted in magenta); (B) interface of Omicron BA.1-ACE2 complex interaction. Residue colors: positively charged (blue): His, Lys, Arg; negatively charged (red): Asp, Glu; neutral (green): Ser, Thr, Asn, Gln; aliphatic (gray): Ala, Val, Leu, Ile, Met; aromatic (purple): Phe, Tyr, Trp; Pro; and Gly (orange).
Figure 6
Figure 6
The molecular dynamics simulation trajectory analysis of protein–protein complexes. Dynamic behavior and stability of the interaction between hACE2 and (A) Omicron BA.2, (B) Omicron BA.1, and (C) Delta variants’ RBDs based on the root-mean-square deviation (RMSD) and the radius of gyration (Rg).
Figure 7
Figure 7
Conformational change and flexibility for each residue of the protein–protein complex of the RBD of Omicron BA.2, Omicron BA.1, and Delta variants with hACE2. (A) Root-mean-square fluctuation (RMSF) plot of hACE2s and (B) RMSF plot of Omicron BA2, BA1, and Delta variants RBD.
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