%0 Journal Article
%A Ansari, Narjes
%A Rizzi, Valerio
%A Carloni, Paolo
%A Parrinello, Michele
%T Water-Triggered, Irreversible Conformational Change of SARS-CoV-2 Main Protease on Passing from the Solid State to Aqueous Solution
%J Journal of the American Chemical Society
%V 143
%N 33
%@ 0002-7863
%C Washington, DC
%I American Chemical Society
%M FZJ-2021-06109
%P 12930 - 12934
%D 2021
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34398611
%U <Go to ISI:>//WOS:000691789500005
%R 10.1021/jacs.1c05301
%U https://juser.fz-juelich.de/record/904539