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


Journal

The journal of physical chemistry letters
ISSN: 1948-7185
Titre abrégé: J Phys Chem Lett
Pays: United States
ID NLM: 101526034

Informations de publication

Date de publication:
06 May 2021
Historique:
pubmed: 27 4 2021
medline: 13 5 2021
entrez: 26 4 2021
Statut: ppublish

Résumé

The catalytic reaction in SARS-CoV-2 main protease is activated by a proton transfer (PT) from Cys145 to His41. The same PT is likely also required for the covalent binding of some inhibitors. Here we use a multiscale computational approach to investigate the PT thermodynamics in the apo enzyme and in complex with two potent inhibitors, N3 and the α-ketoamide

Identifiants

pubmed: 33900080
doi: 10.1021/acs.jpclett.1c00425
pmc: PMC8097931
doi:

Substances chimiques

Antiviral Agents 0
Protease Inhibitors 0
Protons 0
Viral Matrix Proteins 0
membrane protein, SARS-CoV-2 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

4195-4202

Commentaires et corrections

Type : UpdateOf

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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, Tennessee 37996, United States.

Chris Chipot (C)

UMR 7019, Université de Lorraine, Laboratoire International Associé CNRS, 54506 Vandœuvre-lès-Nancy, France.
University of Illinois at Urbana-Champaign, 1110 West Green Street, Urbana, Illinois 61801, United States.

James C Gumbart (JC)

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

Diane L Lynch (DL)

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

Anna Pavlova (A)

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

Jeremy C Smith (JC)

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

Isabella Daidone (I)

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

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Classifications MeSH