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Medicinal-Pharmaceutical Chemistry Commons™
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Full-Text Articles in Medicinal-Pharmaceutical Chemistry
Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta
Mathematics, Physics, and Computer Science Faculty Articles and Research
Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …