Acta Phys. -Chim. Sin. ›› 2005, Vol. 21 ›› Issue (02): 151-155.doi: 10.3866/PKU.WHXB20050208

• ARTICLE • Previous Articles     Next Articles

Homology Modeling and Docking Studies of theα2A-adrenergic Receptor

ZHAO Li-Feng;DING Xiao-Qin;DING Jun-Jie;CHEN Ji-Sheng   

  1. Beijing Institute of Pharmaceutical Chemistry, Beijing 102205
  • Received:2004-07-26 Revised:2004-09-03 Published:2005-02-15
  • Contact: DING Xiao-Qin

Abstract: The properties of several rhodopsin sequences were analyzed by comparing withα2A-adrenergic receptor, and a great similarity was found between bovine rhodopsin andα2A-adrenergic receptor. Therefore transmembrane helices ofα2A-adrenergic receptor were constructed homologically based on the bovine rhodopsin.In the newly constructed structure, a 0.090 nm3 active-site, which was enclosed by several reported active residues, was found. In succession, docking researches of this structure as well as point-mutated ones with inhibitor Yohimbine were conducted using molecular dynamics. The results agree well to the experimental results reported. Furthermore the docking results indicate that a small hydrophobic zone constructed by a tryptophan and two phenylalanines was critical in stabilizing the inhibitor in the active site. At the same time, aspartic acid 113 also weighs heavily to stabilize the inhibitor as a H-bond acceptor.

Key words: Transmembrane protein, α2A-adrenergic receptor, Homology modeling,  Docking, Yohimbine