Rong S B, Zhu Y C, Jiang H L, Zhao S R, Wang Q M, Chi Z Q, Chen K X, Ji R Y
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Zhongguo Yao Li Xue Bao. 1997 Jul;18(4):317-22.
To construct the 3D structural model of mu opioid receptor (mu OR) and study the interaction between mu OR and fentanyl derivatives.
The 3D structure of mu OR was modeled using the bacteriorhodopsin (bRh) as a template, in which 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.
(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 ED50) of the fentanyl derivatives.
This model is helpful for understanding the receptor-ligand interaction and for designing novel mu OR selective ligands.
构建μ阿片受体（μOR）的三维结构模型，并研究μOR与芬太尼衍生物之间的相互作用。
以细菌视紫红质（bRh）为模板对μOR的三维结构进行建模，通过对μOR氨基酸序列与bRh结构之间的比对进行评分，实现bRh和μOR跨膜区（TM）的比对。将芬太尼衍生物对接至μOR的7个螺旋中，并计算结合能。
（1）获得了芬太尼衍生物的受体-配体相互作用模型。（2）在这些模型中，基本结合位点可能是天冬氨酸147（Asp147）和组氨酸297（His297）。Asp147带负电荷的氧与配体带正电荷的铵基团形成了强大的静电和氢键相互作用。而His297带正电荷的氮与配体的羰基氧之间的相互作用较弱。此外，受体与配体之间还存在一些π-π相互作用。（3）受体-配体复合物的结合能与芬太尼衍生物的镇痛活性（-lg ED50）具有良好的相关性。
该模型有助于理解受体-配体相互作用，并有助于设计新型μOR选择性配体。
