@article{APS7456,
author = {Dong-xiang Liu and Hua-liang Jiang and Jing-shan Shen and Wei-liang Zhu and Lei Zhao and Kai-xian Chen and Ru-yun Ji},
title = {Molecular modeling on kappa opioid receptor and its interaction with nonpeptide kappa opioid agonists},
journal = {Acta Pharmacologica Sinica},
volume = {20},
number = {2},
year = {2016},
keywords = {},
abstract = {AIM:
To study the interaction between kappa-opioid receptor and its nonpeptide agonists.
METHODS:
The \"\"conservation patterns\"\" for G-protein coupled receptors (GPCR) were used to determine 7 transmembrane (TM) regions. Taking the crystallographic coordinates of bacteriorhodopsin (BR) as the template, the 3D structural model was constructed for 7 TM of kappa-opioid subtype with molecular mechanics (MM) method. Five highly active nonpeptide kappa-opioid agonists were docked into the 7 helices of kappa-opioid receptor to study the ligand-receptor interaction.
RESULTS:
Four important interactions between U-50488-like agonists and kappa-opioid receptors were drawn according to our modeling study: (1) the protonated pyrrolidine nitrogen of the ligands formed a hydrogen-bond with the carboxyl of Asp138; (2) the carbonyl oxygen of ligands forms a hydrogen bond to the hydroxyl of Ser187; (3) the aryl groups connected to acylamide of the agonists inserted into a hydrophobic cavity enclosed by residues Val239, Val236, Phe235, Val232, Leu186, and Trp183; (4) the pyrrolidine of the ligands in the complexes was surrounded by Ile290, Asp138, Ile194, Ile135, and Cys131.
CONCLUSION:
The proposed interaction mechanism is helpful for further mutant experiments and designing novel potent kappa-opioid agonists.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7456}
}