Mutations of Omicron Variant at the Interface of the Receptor Domain Motif and Human Angiotensin-Converting Enzyme-2

Abstract

The most recent Omicron variant of SARS-CoV-2 has caused global concern and anxiety. The only thing certain about this strain, with a large number of mutations in the spike protein, is that it spreads quickly, seems to evade immune defense, and mitigates the benefits of existing vaccines. Based on the ultra-large-scale ab initio computational modeling of the receptor binding motif (RBM) and the human angiotensin-converting enzyme-2 (ACE2) interface, we provide the details of the effect of Omicron mutations at the fundamental atomic scale level. In-depth analysis anchored in the novel concept of amino acid-amino acid bond pair units (AABPU) indicates that mutations in the Omicron variant are connected with (i) significant changes in the shape and structure of AABPU components, together with (ii) significant increase in the positive partial charge, which facilitates the interaction with ACE2. We have identified changes in bonding due to mutations in the RBM. The calculated bond order, based on AABPU, reveals that the Omicron mutations increase the binding strength of RBM to ACE2. Our findings correlate with and are instrumental to explain the current observations and can contribute to the prediction of next potential new variant of concern.

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

“…A significant increase in this protein’s affinity for hACE2 was observed when mutations were present in the RBD at amino acids 417, 484, and N501 [ 26 ]. Additionally, research on amino-acid–amino-acid bond pair units (AABPU) confirmed that mutation in Omicron increases the affinity of receptor-binding motif (RBM) for ACE2 [ 57 ].…”

Atomic-scale Quantum Chemical Calculation of Omicron Mutations Near Cleavage Sites of the Spike Protein

“…In this sense AABP is an ideal parameter to characterize interactions between different AAs or groups of interacting AAs in biomolecules, i.e., we can consider the AABP to characterize a specific biological unit: the AABP unit (AABPU). In reference [22], AABPU has been thoroughly described and successfully used to investigate the ten mutations at the interface between the receptor domain motif (RBM) and the human ACE2 receptor of the Omicron variant. Hence, in terms of the interactions the AABPU can be considered as distinct structural units in proteins, capable of providing full physical insight into properties such as interatomic interactions, partial charge distributions, size, shape, NL-AA interactions etc.…”

“…The combination of these two different DFT codes, VASP and OLCAO, has been successfully used in a variety of areas, including large biomolecules, organic or inorganic disordered systems, etc. [20][21][22][23][46][47][48][49][50][51].…”

“…Specifically, this study provides detailed computational results to assess the role of each of the 10 OV mutations in SD2-FP and HR1-CH models to ascertain the possible reasons for the rapid infection rate of OV. We employ the novel concept of amino acid-amino acid bond pair (AABP) as specific protein structural unit [22] to quantify and characterize the details of the impact of OV mutations which could help to determine their role in high infectivity.…”

MicroRNAs as Potential Tools for Predicting Cancer Patients’ Susceptibility to SARS-CoV-2 Infection and Vaccination Response

“…Then, the virus affinity to infect certain cells may be related to the multiple organ distribution of ACE2, the functional receptor for SARS-CoV-2 [ 21 ]. Consequently, spike glycoprotein and its RBD are crucial targets for vaccination and therapeutic improvement [ 22 , 23 ].…”