Molecular docking study of the analgesic effect of 17-β estradiol by AMPA receptor
Molecular docking study of the analgesic effect of 17-β estradiol by AMPA receptor
Maryam Azaddar,1,*Amir Abbas Barzegari,2Roghaieh Khakpay,3
1. Instructor of Animal physiology, Department of Biology, Faculty of Basics Sciences, University of Maragheh, Maragheh, Iran 2. Assistant Professor of Animal physiology, Department of Biology, Faculty of Basics Sciences, University of Maragheh, Maragheh, Iran 3. Associate Professor of Animal physiology, Department of Animal Science, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
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 compounds, the eleventh top pose of 17β-estradiol with the code ZINC000028107020 was found strongest docked pose, which demonstrated an important strong affinity with AMPA (–64.253 kcal/mol). Three hydrogen bondings (His-435 D, Ala-745 D, and Cys-436 D) and four steric interactions (His-435 D, Ala-745 D, Cys-436 D, and Lys-752 D) between amino groups of AMPA and this pose were found.
Conclusion: In conclusion, AMPA could constitute an efficient and unexplored target for antinociceptive drug discovery research.