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.