Materials and Methods
Drugs were prepared using Chem Draw 8.0. The 5wrg molecular model (from the PDB) was used in the simulated docking studies for SARS-CoV-2 spike protein as receptor protein. Input protein structures were prepared by adding hydrogen atoms and removing non-functional water molecules. The Autodock software version 1.5.6 (Table 1) and viva (Figure 1) were used for the molecular docking process. The Lamarckian Genetic Algorithm method was used for the global optimum binding position search. The torsion angles of the drugs were identified, hydrogens were added to the macromolecule, bond distances were edited and solvent parameters were added to the enzyme 3D structure. Partial charges were calculated using Gasteiger’s method. Docking parameters were as follows: population size of 150, the maximum number of energy evaluation ranges of 25.0000, the maximum number of generations is 27,000, the mutation rate of 0.02, cross-over rate of 0.8. Other docking parameters were set to the software at its default values. After docking, the drugs were ranked according to their docked energy as implemented in the AutoDock program. A residue ASN 479 in protein binding site was also chosen due to its possible specific hydrogen bonds. This residue was set as flexible residue, while the other residues were kept as rigid residues.
Several 100 cycles of calculation were used to get a final binding position as accurately as possible. The docking procedure was run and the maximum negative Final Docking Energy was calculated. The following parameters were set during docking simulation: population size, 150; and max steps, 100. The center of a grid size were with 40, 40, 40, and 221, 185, 118 points in X, Y, and Z axes respectively. Both were with a grid spacing of 0.0375 nm and were centered at the experimentally determined binding sites.
LIGPLOT software was used for the molecular docking courses. This program automatically generates schematic diagrams of protein-ligand interactions for a given protein in a PDB file (Figure 2). Residues are identical in all seven drugs. The SARS-CoV-2 spike protein structure was constituted of strong hydrogen bonds and hydrophobic interactions, that was observed involving in the protein: drug structure.