Structure preparation and molecular docking:
The experimentally solved SARS CoV-2 RBD-ACE2 complex (PDB ID: 6M0J
solved at 2.45 Å) was obtained from PDB12. The ligand
naltrexone (PubChem CID: 5360515) was extracted from the PubChem
database. An attempt was made to dock to explore the binding mode of
naltrexone onto the binding interface of the RBD-ACE2 complex using
AutoDock version 4.233 and AUTODOCK tools 1.5.6.
Before docking, the protein was prepared by the removal of small
molecules and waters. Then, polar-hydrogen atoms were added to the
structure followed by Gasteiger charges calculation. Ligand centered map
was generated with a spacing of 0.375 Å and grid dimensions of 46 x46x46
Å3 (x-y-z) covering the biding interfaces residues
(which includes the receptor-binding motif viz., RBM) of the complex
(coordinates of central grid point of maps:-34.512, 20.978, 4.521).
Default settings were used for all other parameters while performing
docking with the number of GA run to 100. From the resultant docked
conformations, the top-ranked conformation with the least free energy of
binding, hydrogen-bonding and interatomic-bonding pattern was selected
for further optimization by employing long term MD simulation. PyMOL
(The PyMOL Molecular Graphics System, Version 2.0 Schrödinger, LLC.) and
BIOVIA Discovery Studio Visualizer version4.5 were employed used to
visualize the inter-molecular contacts between naltrexone with RBD-ACE2
complex.