Interaction Analysis of the Spike Protein of Delta and Omicron Variants of SARS-CoV‑2 with hACE2 and Eight Monoclonal Antibodies Using the Fragment Molecular Orbital Method

In the past 2 years, since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple SARS-CoV-2 variants have emerged. Whenever a new variant emerges, considerable time is required to analyze the binding affinity of the viral surface proteins to human angiotensin-conver...

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Bibliographic Details
Published in:Journal of chemical information and modeling 2022-04, Vol.62 (7), p.1771-1782
Main Authors: Hwang, Sungbo, Baek, Seung-Hwa, Park, Daeui
Format: Article
Language:English
Subjects:
Affinity
Angiotensin-Converting Enzyme 2
Antibodies, Monoclonal - metabolism
Binding
Computational Biochemistry
COVID-19
Crystal structure
Humans
Molecular orbitals
Monoclonal antibodies
Mutation
Protein Binding
Proteins
Quantum mechanics
SARS-CoV-2 - genetics
Severe acute respiratory syndrome coronavirus 2
Spike Glycoprotein, Coronavirus - metabolism
Statistical analysis
Viral diseases
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Summary:In the past 2 years, since the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple SARS-CoV-2 variants have emerged. Whenever a new variant emerges, considerable time is required to analyze the binding affinity of the viral surface proteins to human angiotensin-converting enzyme 2 (hACE2) and monoclonal antibodies. To efficiently predict the binding affinities associated with hACE2 and monoclonal antibodies in a short time, herein, we propose a method applying statistical analysis to simulations performed using molecular and quantum mechanics. This method efficiently predicted the trend of binding affinity for the binding of the spike protein of each variant of SARS-CoV-2 to hACE2 and individually to eight commercial monoclonal antibodies. Additionally, this method accurately predicted interaction energy changes in the crystal structure for 10 of 13 mutated residues in the Omicron variant, showing a significant change in the interaction energy of hACE2. S375F was found to be a mutation that majorly changed the binding affinity of the spike protein to hACE2 and the eight monoclonal antibodies. Our proposed analysis method enables the prediction of the binding affinity of new variants to hACE2 or to monoclonal antibodies in a shorter time compared to that utilized by the experimental method.
ISSN:1549-9596
1549-960X
DOI:10.1021/acs.jcim.2c00100