Homology modeling and Molecular docking
The crystal structure of TMPRSS2 is not available, hence the homology
model structure was created from the amino acid sequence of TMPRSS2 with
catalytic domain was retrieved from the UniprotKB (Uniprot Accession
O15393) using Schrodinger homology modeling
interface[23]; in which, Hepsin structure (PDB:
5CE1) was used as a template, based on the sequence similarity
(BLAST).[24] Finally, the modeled structure was
optimized and refined by protein preparation
wizard.[25]. The structure was validated with the
Ramachandran plot (Figure
1S).[ 26]
To understand the binding affinity and the intermolecular interaction of
chosen three drug molecules camostat, nafamostat and
Leupeptin[16,18-21] with the active site amino
acids of the TMPRSS2, the molecular docking has been performed. In prior
to the docking simulation, the three drug molecules were prepared by theLigprep module of Schrodinger software[27]Further, these molecules were docked with the TMPRSS2 by extra precision
mode (XP) incorporated in the induced fit docking (IFD) method. The IFD
resulted in different conformations for each ligand-TMPRSS2 complex.
Based on the top score with the lowest energy conformation and
intermolecular interactions, the ligand-TMPRSS2 complex was selected for
each case and used for further study. PyMOLsoftware[28] was used to analyze the
intermolecular interactions between ligand and protein for the
individual complex.