Insights into the structural properties of SARS-CoV-2 main protease

SARS-CoV-2 is the infectious agent responsible for the coronavirus disease since 2019, which is the viral pneumonia pandemic worldwide. The structural knowledge on SARS-CoV-2 is rather limited. These limitations are also applicable to one of the most attractive drug targets of SARS-CoV-2 proteins - namely, main protease M^pro, also known as 3C-like protease (3CL^pro). This protein is crucial for the processing of the viral polyproteins and plays crucial roles in interfering viral replication and transcription. In fact, although the crystal structure of this protein with an inhibitor was solved, M^pro conformational dynamics in aqueous solution is usually studied by molecular dynamics simulations without special sampling techniques. We conducted replica exchange molecular dynamics simulations on M^pro in water and report the dynamic structures of M^pro in an aqueous environment including root mean square fluctuations, secondary structure properties, radius of gyration, and end-to-end distances, chemical shift values, intrinsic disorder characteristics of M^pro and its active sites with a set of computational tools. The active sites we found coincide with the currently known sites and include a new interface for interaction with a protein partner.