In Silico Substrate-Binding Profiling for SARS-CoV-2 Main Protease (Mpro) Using Hexapeptide Substrates

The SARS-CoV-2 main protease (Mpro) is essential for the life cycle of COVID-19 virus. It cleaves two polyproteins at 11 positions to generate mature proteins virion formation. cleavage site on these known be Leu-Gln↓(Ser/Ala/Gly). A range hexapeptides that follow sequence recognition and was constructed using RDKit libraries complexed with crystal structure Mpro (PDB ID 6XHM) through extensive molecular docking calculations. subset 131 complexes underwent 20 ns dynamics simulations. analyses trajectories from included principal component analysis (PCA), a method compare PCA plots separate developed in terms encoding progression during formed stable as expected, reproducible substrates given extensiveness procedure. Only Lys-Leu-Gln*** (KLQ***) were studied dynamics. In this complexes, identified four classifications protein motions across sequences. KLQ*** illustrated effect changes substrate active site, implications understanding informing development small molecule inhibitors.