Subtle Changes at the RBD/hACE2 Interface During SARS-CoV-2 Variant Evolution: A Molecular Dynamics Study

The SARS-CoV-2 Omicron variants show different behavior compared to the previous variants, especially with respect to the Delta variant, which promotes a lower morbidity despite being much more contagious. In this perspective, we performed molecular dynamics (MD) simulations of the different spike RBD/hACE2 complexes corresponding to the WT, Delta and four Omicron variants. Carrying out a comprehensive analysis of residue interactions within and between the two partners allowed us to draw the profile of each variant by using complementary methods (PairInt, hydrophobic potential, contact PCA). PairInt calculations highlighted the residues most involved in electrostatic interactions, which make a strong contribution to the binding with highly stable interactions between spike RBD and hACE2. Apolar contacts made a substantial and complementary contribution in Omicron with the detection of two hydrophobic patches. Contact networks and cross-correlation matrices were able to detect subtle changes at point mutations as the S375F mutation occurring in all Omicron variants, which is likely to confer an advantage in binding stability. This study brings new highlights on the dynamic binding of spike RBD to hACE2, which may explain the final persistence of Omicron over Delta.

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Publication Details

Journal
Biomolecules
Published
2025-04-07
DOI
https://doi.org/10.3390/biom15040541
Primary Topic
SARS-CoV-2 and COVID-19 Research
Type
article
Field-Weighted Citation Impact
0.00

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article

Subtle Changes at the RBD/hACE2 Interface During SARS-CoV-2 Variant Evolution: A Molecular Dynamics Study

Marie‐Dominique Devignes, Laurent Chaloin, Laurent Vuillon, Bernard Maigret et al.
Biomolecules
SARS-CoV-2 and COVID-19 Research
article

Subtle Changes at the RBD/hACE2 Interface During SARS-CoV-2 Variant Evolution: A Molecular Dynamics Study

Marie‐Dominique Devignes, Laurent Chaloin, Laurent Vuillon, Bernard Maigret, Yasaman Karami, Aria Gheeraert, Isaure Chauvot de Beauchêne, Ivan Rivalta, Dominique Mias‐Lucquin, Vincent Leroux
article en

Abstract

The SARS-CoV-2 Omicron variants show different behavior compared to the previous variants, especially with respect to the Delta variant, which promotes a lower morbidity despite being much more contagious. In this perspective, we performed molecular dynamics (MD) simulations of the different spike RBD/hACE2 complexes corresponding to the WT, Delta and four Omicron variants. Carrying out a comprehensive analysis of residue interactions within and between the two partners allowed us to draw the profile of each variant by using complementary methods (PairInt, hydrophobic potential, contact PCA). PairInt calculations highlighted the residues most involved in electrostatic interactions, which make a strong contribution to the binding with highly stable interactions between spike RBD and hACE2. Apolar contacts made a substantial and complementary contribution in Omicron with the detection of two hydrophobic patches. Contact networks and cross-correlation matrices were able to detect subtle changes at point mutations as the S375F mutation occurring in all Omicron variants, which is likely to confer an advantage in binding stability. This study brings new highlights on the dynamic binding of spike RBD to hACE2, which may explain the final persistence of Omicron over Delta.

BiomoleculesVol. 15(4)
Centre National de la Recherche Scientifique (FR), Université de Montpellier (FR), Laboratoire Lorrain de Recherche en Informatique et ses Applications (FR), Laboratoire de Chimie (FR), Institut de Recherche en Infectiologie de Montpellier (FR), Laboratoire d’Analyse et de Mathématiques Appliquées (FR), Université Savoie Mont Blanc (FR), Université de Lorraine (FR), University of Bologna (IT)
Federation of European Biochemical Societies, Agence Nationale de la Recherche, Centre National de la Recherche Scientifique, Grand Équipement National De Calcul Intensif, Région Occitanie Pyrénées-Méditerranée
Clean water and sanitation
Openalex Percentile: Top 90%
SARS-CoV-2 and COVID-19 Research
DOIOpen Access PDFOpenAlex
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