TY  - JOUR
AU  - Ansari, Narjes
AU  - Rizzi, Valerio
AU  - Carloni, Paolo
AU  - Parrinello, Michele
TI  - Water-Triggered, Irreversible Conformational Change of SARS-CoV-2 Main Protease on Passing from the Solid State to Aqueous Solution
JO  - Journal of the American Chemical Society
VL  - 143
IS  - 33
SN  - 0002-7863
CY  - Washington, DC
PB  - American Chemical Society
M1  - FZJ-2021-06109
SP  - 12930 - 12934
PY  - 2021
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:34398611
UR  - <Go to ISI:>//WOS:000691789500005
DO  - DOI:10.1021/jacs.1c05301
UR  - https://juser.fz-juelich.de/record/904539
ER  -