Tuning Proton Transfer Thermodynamics in SARS-Cov-2 Main Protease: Implications for Catalysis and Inhibitor Design.

Computational Chemistry Covid 19 Main Protease Mpro SARS CoV 2 proton transfer quantum mechanics molecular mechanics thermodynamics

Journal

ChemRxiv : the preprint server for chemistry
ISSN: 2573-2293
Titre abrégé: ChemRxiv
Pays: United States
ID NLM: 101720906

Informations de publication

Date de publication:
06 Nov 2020
Historique:
revised: 06 11 2020
entrez: 17 11 2020
pubmed: 18 11 2020
medline: 18 11 2020
Statut: epublish

Résumé

In this comutational work a hybrid quantum mechanics/molecular mechanics approach, the MD-PMM approach, is used to investigate the proton transfer reaction the activates the catalytic activity of SARS-CoV-2 main protease. The proton transfer thermodynamics is investigated for the apo ensyme (i.e., without any bound substrate or inhibitor) and in the presence of a inhibitor, N3, which was previously shown to covalently bind SARS-CoV-2 main protease.

Identifiants

pubmed: 33200115
doi: 10.26434/chemrxiv.13200227
pii: 13200227
pmc: PMC7668740
doi:

Types de publication

Preprint

Langues

eng

Commentaires et corrections

Type : UpdateIn

Déclaration de conflit d'intérêts

No conflict of interest to declare

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Auteurs

Laura Zanetti-Polzi (L)

Center S3, CNR Institute of Nanoscience, Via Campi 213/A, I-41125 Modena, Italy.

Micholas Dean Smith (MD)

Department of Biochemistry, Molecular and Cellular Biology, The University of Tennessee, Knoxville. 309 Ken and Blaire Mossman Bldg. 1311 Cumberland Avenue, Knoxville, TN 37996, United States.

Chris Chipot (C)

UMR 7019, Universite de Lorraine, Laboratoire International Associe CNRS.
University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, IL, 61801, United States.

James C Gumbart (JC)

School of Physics, Georgia Institute of Technology, Atlanta GA 30332, United States.

Diane L Lynch (DL)

School of Physics, Georgia Institute of Technology, Atlanta GA 30332, United States.

Anna Pavlova (A)

School of Physics, Georgia Institute of Technology, Atlanta GA 30332, United States.

Jeremy C Smith (JC)

UT/ORNL Center for Molecular Biophysics, Biosciences Division, Oak Ridge National Laboratory, TN 37831, United States.
Department of Biochemistry, Molecular and Cellular Biology, The University of Tennessee, Knoxville. 309 Ken and Blaire Mossman Bldg. 1311 Cumberland Avenue, Knoxville, TN 37996, United States.

Isabella Daidone (I)

Department of Physical and Chemical Sciences, University of L'Aquila, Via Vetoio, I-67010 L'Aquila, Italy.

Classifications MeSH