Release 2016 2

The X-ray crystallographic structure of EGFR was obtained from the PDB server (PDB code: 4HJO) [39 (link)] and optimized for molecular docking studies in the protein preparation module of Schrödinger software. Optimized Potential Liquid Simulations (OPLS_2005) force field was used at physiological pH in ligand preparation module of Schrödinger software for preparation of compound 10 and erlotinib with energy minimization. Finally, Grid Generation and Glide/XP docking protocols were applied, respectively in molecular docking simulations (Schrödinger Release 2016-2: Schrödinger, LLC, New York, NY, USA).

Ligands were prepared in the Ligprep program (Schrödinger, New York, NY, United States) [45 ] employing the OPLS_2005 force field, with protonation states predicted using Epik at pH 9.5 ± 2.0. The West Nile Virus protease NS2B-NS3 PDB code 2IJO [46 (link)], chosen as the receptor, was prepared with the Protein Preparation Wizard (Schrödinger, New York, NY, United States), with removal of all waters and addition of hydrogens based on PROPKA calculations at pH 9.5. Docking calculations were performed with the Glide software (Schrödinger, New York, NY, United States) [47 (link), 48 ], employing the Induced Fit docking methodology [49 (link)] and Glide SP. All the software packages used are part of the Schrödinger Release 2016–2 package (Schrödinger, New York, NY, United States) [50 ]. A spherical grid with 12 Å radius was centered in the Isoleucine 123 residue so that the active site was fully included within the grid. All residues within 5 Å from the center were considered flexible. Docking results were ranked based on their docking score and the top ranking poses for each compound were analyzed with the Maestro 10.6 software (Schrödinger, New York, NY, United States) [51 ].