Fig. 7.

Results of a 100 ns (ns) MD simulation of compound VIII. (A) Schematic 2D representation of bound ligand interactions throughout the simulation. (B) Root mean square fluctuation between the binding site of the target protein and the interacting ligand. (C) Critical protein–ligand contacts of amino acid side chain residues with the interaction properties. (D) Root mean square deviations difference between the Main protease (3CLPro) and bound ligand VIII (<4 Å). The graph was obtained for the RMSF value of ligand (purple line) from the protein backbone (green line). The docked complex quickly stabilized to a very low energy state in 8–9 ns. After that, the ligand was highly stable throughout the simulation except for getting dislodged at 83 ns due to the trifluoride group being pulled by a distant Glu166. The altered state has a rapid decrease in energy and highlights the docking stability as well as the scope of improvement to further strengthen the interactions.