Introduction: Molecular modeling is a powerful tool for studying structure-
activity relationships in the research-based pharmaceutical industry.
Pharmacodynamic data such as strength, affinity, effectiveness, and
selectivity are studied by applying these methods. Before performing
experimental experiments, the interaction of chemical compounds with
proteins can be investigated using computational methods, and after making
sure that the compounds are more likely to bind to the target, they can be
tested in the laboratory or in living systems. According to the results of our
previous research, the analgesic effect of intra-paragigantocellularis lateralis
17β-estradiol on formalin-induced inflammatory pain might be mediated via
AMPA receptors in Male Rats. This study investigated the antinociceptive role
of 17β-estradiol and its interaction with the AMPA receptor by molecular
docking.
Methods: MPA receptor PDB file was downloaded from Protein Data Bank
(PDB) with the code 6NJN. Also, 20 SDF files for 17β-estradiol were
downloaded from the ZINC database. The active site was delimited based on
reported residues at PDB and complemented with searching of close residues
until 6 Å far crystallized protein supported by Molegro Virtual Docker Tools.
Thus, active site was constituted by following residues: 6NJN (chain A); Val-
484, Leu-483, Glu-487, 6NJN (chain D); Gln-766, Lys-762, Leu-763, Leu-761,
Lys-734, Leu-748, Leu-742, Glu-731, His-735, Asn-747, Ala-744, Val-746,
Val-760, Ala-749, Ala-745, IIe-732, Cys-736, Gly-737. All molecular docking
assays were carried out using flexible residues. Ligand and protein were
docked employing Molegro Virtual Docker. In the strongest docked pose,
residual interaction maps were obtained with Molegro Molecular Viewer for
compounds that exhibited the highest affinity energy.
Results: The results of molecular docking were first analyzed in terms of
affinity energy. 20 compounds of 17β-estradiol were tested via molecular
docking. From docked