物理化学学报 >> 2005, Vol. 21 >> Issue (02): 151-155.doi: 10.3866/PKU.WHXB20050208

研究论文 上一篇    下一篇

α2A肾上腺素受体的同源模建及与Yohimbine的对接研究

赵立峰;丁晓琴;丁俊杰;陈冀胜   

  1. 北京药物化学研究所,北京 102205
  • 收稿日期:2004-07-26 修回日期:2004-09-03 发布日期:2005-02-15
  • 通讯作者: 丁晓琴 E-mail:dingxq@cetin.net.cn

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 E-mail:dingxq@cetin.net.cn

摘要: 通过对比多个与α2A-肾上腺素受体同属G-蛋白偶联受体的视紫红质蛋白序列,选择以相似性最大的牛视紫红质蛋白为模板,同源模建了α2A-肾上腺素受体的跨膜结构,并在结构中找到了体积为0.090 nm3,已被报导的活性残基包围的活性位点.运用分子力学与动力学方法研究了此结构突变前后与抑制剂Yohimbine的对接情况,得到了与文献报道相吻合的结果.同时对接研究结果发现,在α2A-肾上腺素受体的结合位点周围的一个由色氨酸和两个苯丙氨酸组成的局部疏水区对抑制剂有稳定作用,并且天冬氨酸113作为氢键受体也对稳定抑制剂有重要作用.

关键词: 跨膜蛋白, α2A-肾上腺素受体, 同源模建, 对接, Yohimbine

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