pH Effect on the Dynamics of SARS-CoV-2 Main Protease (Mpro)

The SARS-CoV-2 main protease (M pro ) is a crucial enzyme responsible for the maturation of novel coronavirus, thus it serves as an excellent target for drug discovery. SARS-CoV-2 is found to have similarity with SARS-CoV, which showed conformational changes upon varying pH. There is no study till date on how pH change affect the conformtional flexibilty of SARS-CoV-2 M pro , therefore, we attempt to find the effect of pH variation through constant pH molecular dynamics simulation studies. Protein is found to be most stable at neutral pH and as pH turns basic protein structure becomes most destabilized. Acidic pH also tends to change the structural properties of M pro . Our study provides evidence that the flexibility of M pro is pH dependent like SARS-CoV M pro .