Molecular modeling of mu opioid receptor and receptor-ligand interaction
Rong, S.B.; Zhu, Y.C.; Jiang, H.L.; Zhao, S.R.; Wang, Q.M.; Chi, Z.Q.; Chen, K.X.; Ji, R.Y.
Zhongguo Yao Li Xue Bao 18(4): 317-322
1997
ISSN/ISBN: 0253-9756 PMID: 10072913 Document Number: 473571
AIM: To construct the 3D structural model of mu opioid receptor (mu-OR) and study the interaction between mu-OR and fentanyl derivatives. METHODS: The 3D structure of mu-OR was modeled using the bacteriorhodopsin (bRh) as a template, in wbich the alignments of transmembrane (TM) of bRh and mu-OR were achieved by scoring the alignment between the amino acid sequence of mu-OR and the structure of bRh. The fentanyl derivatives were docked into the 7 helices of mu-OR and the binding energies were calculated. RESULTS: (1) The receptor ligand interaction models were obtained for fentanyl derivatives. (2) In these models, the fundamental 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 interactions. Whereas the interactions between the positively charged nitrogen of His297 and the carbonyl oxygen of ligand were weak. In addition, there were some pi - pi interactions between the receptor and the ligand. (3) The binding energies of the receptor-ligand complexes had a good correlation with the analgesic activities (-lg ED-50) of the fentanyl derivatives. CONCLUSION: This model is helpful for understanding the receptor-ligand interaction and for designing novel mu-OR selective ligands.