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Structural_Analysis_COVID19_29May2020.pdf (1.69 MB)
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Structural Analysis of COVID-19 Main Protease and its Interaction with the Inhibitor N3

preprint
submitted on 30.05.2020 and posted on 01.06.2020 by Tika Ram Lamichhane, Madhav Prasad Ghimire
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.

History

Email Address of Submitting Author

madhav.ghimire@cdp.tu.edu.np

Institution

Tribhuvan University

Country

Nepal

ORCID For Submitting Author

0000-0003-2783-4008

Declaration of Conflict of Interest

No conflict of interest

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