Electrostatic Features for the Receptor Binding Domain of SARS-COV-2 Wildtype and Its Variants. Compass to the Severity of the Future Variants with the Charge-Rule.
J Phys Chem B
; 126(36): 6835-6852, 2022 09 15.
Article
em En
| MEDLINE
| ID: mdl-36066414
Electrostatic intermolecular interactions are important in many aspects of biology. We have studied the main electrostatic features involved in the interaction of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein with the human receptor Angiotensin-converting enzyme 2 (ACE2). As the principal computational tool, we have used the FORTE approach, capable to model proton fluctuations and computing free energies for a very large number of protein-protein systems under different physical-chemical conditions, here focusing on the RBD-ACE2 interactions. Both the wild-type and all critical variants are included in this study. From our large ensemble of extensive simulations, we obtain, as a function of pH, the binding affinities, charges of the proteins, their charge regulation capacities, and their dipole moments. In addition, we have calculated the pKas for all ionizable residues and mapped the electrostatic coupling between them. We are able to present a simple predictor for the RBD-ACE2 binding based on the data obtained for Alpha, Beta, Gamma, Delta, and Omicron variants, as a linear correlation between the total charge of the RBD and the corresponding binding affinity. This "RBD charge rule" should work as a quick test of the degree of severity of the coming SARS-CoV-2 variants in the future.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
SARS-CoV-2
/
COVID-19
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Phys Chem B
Assunto da revista:
QUIMICA
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
Estados Unidos