Molecular dynamics (MD) simulation studies of SARS-CoV-2 Mpro and SARS-CoV-2 Mpro -SRT2183 complex

All-atom MD simulations were performed on SARS-CoV-2M^pro alone and in complex with ligand “SRT2183” (best ligand sorted on the basis of binding free energy and ligand–protein interactions) to determine conformational dynamics in the aqueous environment. The trajectories of the SARS-CoV-2 M^pro and SARS-CoV-2 M^pro-SRT2183 complex were studied through 50 ns of MD simulations at 300 K using GROMOS96 force-field in GROMACS 5.1.2. The topology files of the SRT2183 were computed using PRODRG server (an external web plate form). Topology files of SRT2183 were merged with the protein topology to generate the SARS-CoV-2 M^pro-SRT2183 complex system. Both systems were solvated in a cubic box with the Simple Point Charge (spc216) water model to simulate aqueous surroundings (Goel et al. 2011; Lagunin et al. 2000). Both systems were subjected to energy minimization using 1500 steps of the steepest descent method for 100 ps to remove their possible steric clashes. The temperature of both systems was subsequently increased from 0 to 300 K during the equilibration period of 100 ps at a constant volume under periodic boundary conditions with a stable environment of 1-bar pressure. Various geometrical properties of the systems, such as root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and solvent accessible surface area (SASA), were determined using g_rmsd, g_rmsf, g_gyrate, and g_sas programs. All the graphs were plotted using Xmgrace tool.