In silico studies of rs1799971 (A118G) OPRM1 gene structural variant binding to morphine as an opioid addiction substrate

Introduction: According to the previous studies, A118G has showed a critical role in the association studies ofmu-opioid receptor 1(OPRM1, MOR). We aimed to investigate homology modeling and docking analyses ofrs1799971 (A118) in binding to morphine as an opioid addiction substrate for the first time.Methods: The tertiary structures of human MOR protein in wild-type (Asn40) and mutant (Asp40) alleles ofrs1799971 (A118G) were modeled by the chosen template (PDB ID: 4DJH) through Swiss Model and Phyre2online softwares. Then, best models (from Phyre2) were built after energy minimization by Swiss-PdbViewerDeepView ver. 4.1.0 software. The structures of designed models were then validated using RAMPAGE andProSA softwares. Final 3-D models were visualized by Autodock ver. 1.5.6. To prepare the ligand for docking,energy minimization of ligands was performed using Hyperchem professional tool ver. 8.0.8. Active site ofOPRM1 was predicted by COACH. Best comformation through 10 built comformations was opted based on thelowest binding energy and H-Bonds in cluster. Finally, dominant and recesive complexes with same ligand werecompared to each other.Results: In silico analyses of OPRM1 protein with morphine as ligand represented that the best comformation ofmorphine had more binding affinity to Asp40 (binding Energy=-7.93 kcal/mol with 3 Hydrogen bondsformation) compared to Asn40 model (binding Energy=-7.43 kcal/mol with 1 H-bond formation).Conclusion: Cosequently, genotyping of A118G as a remarkable marker of opioid addiction may be helpful inmorphine administration and treatment among populations which have shown significant associations of A118Gwith opioid addiction.

کلیدواژه ها:

A118G ، Homology modeling ، Docking ، Morphine ، Addiction