1. Water-Triggered, Irreversible Conformational Change of SARS-CoV-2 Main Protease on Passing from the Solid State to Aqueous Solution
- Author
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Valerio Rizzi, Narjes Ansari, Paolo Carloni, and Michele Parrinello
- Subjects
Conformational change ,medicine.medical_treatment ,Protein subunit ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Molecular Dynamics Simulation ,Crystallography, X-Ray ,Biochemistry ,Catalysis ,Viral Matrix Proteins ,Molecular dynamics ,Colloid and Surface Chemistry ,medicine ,Molecule ,Humans ,Symmetry breaking ,Protein Structure, Quaternary ,Protease ,Aqueous solution ,Hydrogen bond ,Chemistry ,SARS-CoV-2 ,Communication ,COVID-19 ,Water ,Hydrogen Bonding ,General Chemistry ,Protein Subunits ,Chemical physics ,Biophysics - Abstract
The main protease from SARS-CoV-2 is a homodimer. Yet, a recent 0.1 ms long molecular dynamics simulation shows that it readily undergoes a symmetry breaking event on passing from the solid state to the aqueous solution. As a result, the subunits present distinct conformations of the binding pocket. By analysing this long time simulation, here we uncover a previously unrecognised role of water molecules in triggering the transition. Interestingly, each subunit presents a different collection of long-lived water molecules. Enhanced sampling methods performed here, along with machine learning approaches, further establish that the transition to the asymmetric state is essentially irreversible.
- Published
- 2021