MOLECULAR MODELING OF MU-OPIOID RECEPTOR AND RECEPTOR-LIGAND INTERACTION

AIM: To construct the 3D structural model of mu opioid receptor (mu OR ) and study the interaction between mu OR and fentanyl derivatives. ME THODS: The 3D structure of mu OR was modeled using the bacteriorhodops in (bRh) as a template, in which the alignments of transmembrane (TM) of bRh and mu OR were achieved by scoring the alignment between the am ino acid sequence of mu OR and the structure of bRh. The fentanyl deri vatives were docked into the 7 helices of mu OR and the binding energi es were calculated. RESULTS: (1) The receptor-ligand interaction model s were obtained for fentanyl derivatives. (2) In these models, the fun damental binding sites were possibly Asp147 and His297. The negatively charged oxygen of Asp147 and the positively charged ammonium group of ligand formed the;potent electrostatic and hydrogen-binding interacti ons. Whereas the interactions;between the positively charged nitrogen of His297 and the carbonyl oxygen of ligand were weak. In addition, th ere were some R-R interactions between the receptor and the ligand. (3 ) The binding energies of the receptor-ligand complexes had a good cor relation with the analgesic activities (-1g ED50) of the fentanyl deri vatives. CONCLUSION: This model is helpful for understanding the recep tor-ligand interaction and for designing novel mu OR selective ligands .