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Here, we analyze the structural
features of a ligand binding domain (LBD) in COVID-19 main protease (MP)
followed by the interactions between the inhibitor N3 and MP-LBD residues
through the molecular dynamics simulations. The time based changes in physical
parameters that includes root mean square deviation (RMSD), root mean square
fluctuation (RMSF), radius of gyration (RG), dihedral distributions, residue
velocity, radial distribution function (RDF) and H-bonding signify the degrees
of folding states in MP-N3 complex formed by the superimposed b-barrels and flexible a-helices. Sharp and flat RDF peaks observed for the atom pairs dictate the
flexibility of MP-LBD residues during their interactions with N3. In spite of
larger solvent accessibility of N3, it interacts strongly with the LBD residues
resulting in H-bonding. Among the LBD residues, GLU166 is found to have the
lowest residue velocity that offers the sharp RDF peaks for three H-bonding
atom pairs nearly at 2 Å radial distance, whereas GLY143 has the highest value
of residue velocity giving rise to a flat RDF peak for the MP-N3 atom pair.
Furthermore, electrostatic and van der Waals interaction energies between N3
and MP-LBD residues are noted to have the negative values. All these parameters
explain the binding nature of N3 like inhibitors to the substrate binding sites
of COVID-19 main protease. These analysis are expected to be a possible route
applicable in drug designing mechanism to restrict the viral replication and
transcription of COVID-19.