Water-Triggered, Irreversible Conformational Change of SARS-CoV-2 Main Protease on Passing from the Solid State to Aqueous Solution.
J Am Chem Soc
; 143(33): 12930-12934, 2021 08 25.
Article
in English
| MEDLINE | ID: covidwho-1358340
Preprint
This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
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This scientific journal article is probably based on a previously available preprint. It has been identified through a machine matching algorithm, human confirmation is still pending.
See preprint
ABSTRACT
The main protease from SARS-CoV-2 is a homodimer. Yet, a recent 0.1-ms-long molecular dynamics simulation performed by D. E. Shaw's research group shows that it readily undergoes a symmetry-breaking event on passing from the solid state to aqueous solution. As a result, the subunits present distinct conformations of the binding pocket. By analyzing this long simulation, we uncover a previously unrecognized role of water molecules in triggering the transition. Interestingly, each subunit presents a different collection of long-lived water molecules. Enhanced sampling simulations performed here, along with machine learning approaches, further establish that the transition to the asymmetric state is essentially irreversible.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Water
/
Viral Matrix Proteins
/
SARS-CoV-2
Limits:
Humans
Language:
English
Journal:
J Am Chem Soc
Year:
2021
Document Type:
Article
Affiliation country:
Jacs.1c05301
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