咪唑啉类药物与钾离子通道Kir6.2相互作用的分子对接研究

高等学校化学学报 ›› 2009, Vol. 30 ›› Issue (11): 2268.

咪唑啉类药物与钾离子通道Kir6.2相互作用的分子对接研究

张蕊^1,3, 凌宝萍², 孟祥华², 王志国^1,3, 张长桥², 刘永军^1,2, 刘成卜²

1. 中国科学院西北高原生物研究所, 西宁 810001;
2. 山东大学化学与化工学院, 济南 250100;
3. 中国科学院研究生院, 北京 100049

收稿日期:2008-11-17 出版日期:2009-11-10 发布日期:2009-11-10
通讯作者: 刘永军, 男, 博士, 教授, 博士生导师, 主要从事理论化学方面的研究. E-mail: yongjunliu1@sdu.edu.cn; 刘成卜, 男, 博士, 教授, 博士生导师, 主要从事理论化学方面的研究. E-mail: cbliu@sdu.edu.cn
基金资助:
国家自然科学基金(批准号： 30873158)和国家“九七三”计划(批准号: 2008CB13617508)资助.

Docking Studies on the Interaction of Imidazolines and Potassium Ion Channel-Kir6.2

ZHANG Rui^1,3, LING Bao-Ping², MENG Xiang-Hua², WANG Zhi-Guo^1,3, ZHANG Chang-Qiao², LIU Yong-Jun^1,2*, LIU Cheng-Bu^2*

1. Northwest Institute of Plateau Biology, Chinese Academy of Sciences, Xining 810001, China;
2. School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China;
3. Graduate University of Chinese Academy of Science, Beijing 100049, China

Received:2008-11-17 Online:2009-11-10 Published:2009-11-10
Contact: LIU Yong-Jun, E-mail: yongjunliu1@sdu.edu.cn; LIU Cheng-Bu, E-mail: cbliu@sdu.edu.cn
Supported by:
国家自然科学基金(批准号： 30873158)和国家“九七三”计划(批准号: 2008CB13617508)资助.

摘要/Abstract

摘要：

运用AutoDock4软件进行了分子对接研究, 得到了7种咪唑啉药物分子与Kir6.2的作用位点, 并发现了2个活性位点区域; 依法可生(Efaroxan)、可乐定(Clonidine)、西苯唑啉(Cibenzoline)和Bl11282位于残基H175, K67和W68形成的活性口袋中, 主要作用方式为氢键相互作用; 而Rx871024、烯丙尼定(Alinidine)和Ly389382位于残基F168, M169和I296形成的疏水口袋中, 在Kir6.2的通道孔中央, 没有氢键形成, 主要作用为疏水相互作用. 咪唑啉类药物与Kir6.2相互作用活性位点的理论预测将有助于该药物在胰腺β细胞中调控胰岛素分泌机制的研究.

关键词: 咪唑啉类药物; KATP通道; Kir6.2; 分子对接; 结合位点

Abstract:

Kir6.2, a key component of the ATP-sensitive potassium channel(K_ATP), can directly interact with imidazolines, a kind of potential antidiabetic drug. This paper explored the interaction of Kir6.2 with imidazoline molecules by applying AutoDock software. The docking results reveal the binding sites of the seven imidazolines on Kir6.2. For Efaroxan, Clonidine, Cibenzoline and Bl11282, polar residues, H175, K67and W68, constitute the binding pocket; while Rx871024, Alinidine and Ly389382, lies in a hydrophobic pocket which is composed of nonpolar residues, F168, M169 and I296. Efaroxan, Clonidine, Cibenzoline and Bl11282 interact with Kir6.2 mainly by forming hydrogen bonds, but for Rx871024, Alinidine and Ly389382, the hydrophobic interaction is the most important mode of action. These binding sites and the interaction modes can interpret the inhibition of these imidazoline drugs to some extent, and this research may provide theoretical support in the pharmacological study of imidazolines regulating the secretion of insulin.

Key words: Imidazolines; KATP channel; Kir6.2; Docking; Binding site

TrendMD:

张蕊, 凌宝萍, 孟祥华, 王志国, 张长桥, 刘永军, 刘成卜. 咪唑啉类药物与钾离子通道Kir6.2相互作用的分子对接研究. 高等学校化学学报, 2009, 30(11): 2268.

ZHANG Rui, LING Bao-Ping, MENG Xiang-Hua, WANG Zhi-Guo, ZHANG Chang-Qiao, ....... Docking Studies on the Interaction of Imidazolines and Potassium Ion Channel-Kir6.2. Chem. J. Chinese Universities, 2009, 30(11): 2268.

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