امیر عباس برزگری سرخه

Background and Aim: Molecular modeling is a powerful tool for the study of structure-activity relationships (SAR) in the research-based pharmaceutical industry. According to the results of our previous research, the analgesic effect of intra-paragigantocellularis lateralis 17β-estradiol on the formalin-induced inflammatory pain might be mediated via GABAA receptors in Male Rats. This study investigated the antinociceptive role of 17β-estradiol and its interaction with the GABAA receptor by molecular docking. Methods: GABAA receptor pdb file was downloaded from Protein Data Bank (PDB) with the code 6DW1. 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: 6DW1 (chain D); Asp-120, Trp-123, IIe-124, Thr-146, Lys-118, Pro-127, Asn-128, His-122, Arg-144, Ala-121, Thr-125, Thr-126, and 6DW1 (chain C); Asn-110, His-109, Ala-108, Gly-103, Lys-104, Lys-105, Ser-106, Val-107, Leu-132. All molecular docking assays were carried out using flexible residues. Ligand and protein were docked employing Molegro Virtual Docker. The strongest docked pose, residual interactions 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 compounds, the second top pose of 17β-estradiol with the code ZINC000058475582 was found strongest docked pose, which demonstrated to achieve an important strong affinity with GABAA (–80.6682 kcal/mol). Two hydrogen bondings (Lys-104 C, and His-122 D) and four steric interactions (Trp- 123 D, His-122 D, Ser-106 C, and Lys-104 C) between amino groups of GABAA and this pose wer