Molecular dynamics simulation perception study of the binding affinity performance for main protease of SARS-CoV-2

Like common cold and flu, SARC-CoV-2 virus spreads by droplets of sneezes or coughs which virus affects people of various age groups. Today, this virus is almost distributed all over the world. Since binding process plays a crucial role between host and receptor, therefore, we studied the molecules intended toward inhibition process through molecular docking and molecular dynamics simulation process. From the molecular docking study, it is noteworthy that remdesivir shows better binding affinity toward the main protease of SARS-CoV2 compared to other studied drugs. Within studied phytochemicals, carnosic acid shows better binding poses toward main protease of SARS-CoV2 among studied phytochemicals. The amino acid residues GLN110 and PHE294 were almost found in all the studied interactions of drugs and phytochemicals with main protease of SARS-CoV-2. Furthermore, the results show a larger contribution of the Van der Waals energies as compared to others like electrostatic energies suggesting that ligands at the binding pocket are predominantly stabilized by hydrophobic interactions. The conformational change during ligand binding was predicted from Gibbs free energy landscape analysis through molecular dynamics simulation. We observed that, there were two main free energy basins for both docked carnosic acid complex and for docked remdesivir complex, only one main free energy basin was found in the global free energy minimum region. Communicated by Ramaswamy H. Sarma

Automated summary

This study investigated the binding affinity and interactions of various drugs and phytochemicals with the main protease of SARS-CoV-2 through molecular docking and molecular dynamics simulation. The results showed that remdesivir exhibited strong binding affinity, while carnosic acid demonstrated the best binding poses. The presence of specific amino acid residues, GLN110 and PHE294, in all studied interactions suggested their importance in ligand binding. The study also revealed the predominant role of hydrophobic interactions in stabilizing the ligands at the binding pocket.