Interfacial Water Many-Body Effects Drive Structural Dynamics and Allosteric Interactions in SARS-CoV-2 Main Protease Dimerization Interface.
J Phys Chem Lett
; 12(26): 6218-6226, 2021 Jul 08.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1387122
ABSTRACT
Following our previous work ( Chem. Sci. 2021, 12, 4889-4907), we study the structural dynamics of the SARS-CoV-2 Main Protease dimerization interface (apo dimer) by means of microsecond adaptive sampling molecular dynamics simulations (50 µs) using the AMOEBA polarizable force field (PFF). This interface is structured by a complex H-bond network that is stable only at physiological pH. Structural correlations analysis between its residues and the catalytic site confirms the presence of a buried allosteric site. However, noticeable differences in allosteric connectivity are observed between PFFs and non-PFFs. Interfacial polarizable water molecules are shown to appear at the heart of this discrepancy because they are connected to the global interface H-bond network and able to adapt their dipole moment (and dynamics) to their diverse local physicochemical microenvironments. The water-interface many-body interactions appear to drive the interface volume fluctuations and to therefore mediate the allosteric interactions with the catalytic cavity.
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Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Agua
/
Proteínas de la Matriz Viral
/
Simulación de Dinámica Molecular
/
SARS-CoV-2
Tipo de estudio:
Estudio experimental
Límite:
Humanos
Idioma:
Inglés
Revista:
J Phys Chem Lett
Año:
2021
Tipo del documento:
Artículo
País de afiliación:
ACS.JPCLETT.1C01460
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