COMPARISON BETWEEN INTERACTION OF QUERCETIN AND MORPHINE WITH MU OPIOID RECEPTOR: IN SILICO EVALUATION BY DOCKING METHOD

Background and Aim : Quercetin, is a plant-derived flavonoid found in fruits and vegetables and is found in a variety of daily foods such as grapes, onions, and tea. A growing body of evidence suggests that quercetin modulates the effect of morphine on central nervous system. Here we examine the possible interaction between quercetin and Mu opioid receptor. Methods : The best Mu opioid receptor pdb structure was found from PDB database (PDB ID: 5C1M, Resolution: 2.1 Å and organism: Mus musculus). Structure validation was performed by PROCHECK, Most favoured regions: 93.0% . We used YASARA Energy Minimization Server to energy minimization. The structure validation was performed again and this time most favoured regions was 94.1%. then, we used this energy minimized structure for docking. The molecular structures of the Ligands were obtained from PubChem (Quercetin CID: 5280343 and Morphine CID: 5288826). Ligand binding site was found (using discovery studio Visualizer Client). Two residues (HIS54 and ASP147) were selected for flexible portion of the receptor. Docking was performed using AutoDock4, MGL Tools 1.5.6.Results : The binding energy between mu receptor and quercetin was -11.04 kcal/mol. This parameter was -7.96 kcal/mol between morphine and receptor. The inhibition constant (Ki) of quercetin and morphine in interaction with mu receptor were 8.09 nM and 1.47 µM, respectively. Conclusion : Mu receptor had lower binding energy in interaction with quercetin than morphine. And quercetin showed many lower Ki than morphine. It depicts that receptor-quercetin complex is more stable. So, it seems that the using of quercetin in studies to finding a substitute for morphine and decreasing its side effects will be useful.

Keywords:

Docking , Mu opioid receptor , Morphine , Quercetin