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  

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

作　　者：张蕊[1,2] 凌宝萍[3] 孟祥华[3] 王志国[1,2] 张长桥[3] 刘永军[1,3] 刘成卜[3] 

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

出　　处：《高等学校化学学报》2009年第11期2268-2273,共6页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:30873158);国家“九七三”计划(批准号:2008CB13617508)资助

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.Kir6.2, a key component of the ATP-sensitive potassium channel （KATP） , can directly interact with imidazolines, a kind of potential antidiabetic drug. This paper explored the interaction of Kit6.2 with imidazoline molecules by applying AutoDock software. The docking results reveal the binding sites of the seven imidazolines on Kit6.2. For Efaroxan, Clonidine, Cibenzoline and B111282, 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 B111282 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.

关 键 词：咪唑啉类药物 KATP通道 KIR6.2 分子对接 结合位点 

分 类 号：O641[理学—物理化学]