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@ARTICLE{Ansari:904539,
author = {Ansari, Narjes and Rizzi, Valerio and Carloni, Paolo and
Parrinello, Michele},
title = {{W}ater-{T}riggered, {I}rreversible {C}onformational
{C}hange of {SARS}-{C}o{V}-2 {M}ain {P}rotease on {P}assing
from the {S}olid {S}tate to {A}queous {S}olution},
journal = {Journal of the American Chemical Society},
volume = {143},
number = {33},
issn = {0002-7863},
address = {Washington, DC},
publisher = {American Chemical Society},
reportid = {FZJ-2021-06109},
pages = {12930 - 12934},
year = {2021},
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.},
cin = {IAS-5 / INM-9},
ddc = {540},
cid = {I:(DE-Juel1)IAS-5-20120330 / I:(DE-Juel1)INM-9-20140121},
pnm = {5241 - Molecular Information Processing in Cellular Systems
(POF4-524)},
pid = {G:(DE-HGF)POF4-5241},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:34398611},
UT = {WOS:000691789500005},
doi = {10.1021/jacs.1c05301},
url = {https://juser.fz-juelich.de/record/904539},
}