2.4. Molecular docking and screening

Flexible docking was performed to evaluate the docking score, Glide score, and Glide e-model of all the prepared ligands against the predicted binding site of SARS-CoV-2-RdRp (PDB ID: 7BTF) using Glide v8.3, Schrodinger, LLC, New York, NY, 2019-2. Glide generates multiple poses for every ligand which are initially filtered by the spatial fit on the protein grid or active site and are checked for the complementarity of interaction using the ChemScore function.

The poses that pass the initial filter were minimized with respect to the receptor grid using OPLS-AA nonbonded ligand–receptor interaction energy. Once the energy is calculated Glide score multiligand scoring function assigned scores to the poses. GLIDE docking was carried out in standard-precision (SP) mode, and the molecules that bind to the receptors with good docking scores and negative binding energy were used for further analysis.

Docking results were assessed based on the scoring function given by Glide score or Glide G-score, which can be represented as:

GScore = 0.065 × Vander Waals energy + 0.130 × Coulomb energy + Lipo + H bond + Metal + BuryP + RotB + Site where Lipo = hydrophobic interactions, Metal = metal binding, BuryP = buried polar group penalty, RotB = penalty for freezing rotatable bonds, and Site = polar interactions existing in the active site represented.

Analysis of amodiaquine, hydroxychloroquine, and chloroquine in comparison to ATP substrate, was carried out based on docking scores and involved interacting residues of the active site.