水分子在尼古丁与α4β2烟碱乙酰胆碱受体结合过程中的作用研究  

Role of the Water Molecules on the Binding of the Nicotine to the α4β2 Nicotinic Acetylcholine Receptor

作　　者：刘璐 赵紫彤 初鑫 于日磊[1,2] LIU Lu;ZHAO Zi-tong;CHU Xin;YU Ri-li(Key Laboratory of Marine Drugs,Ministry of Education,School of Medicine and Pharmacy,Ocean University of China,Qingdao 266003,China;Laboratory for Marine Drugs and Bioproducts of Qingdao National Laboratory for Marine Science and Technology,Qingdao 266237,China)

机构地区：[1]中国海洋大学海洋药物教育部重点实验室,医药学院,山东青岛266003 [2]青岛海洋科学与技术国家实验室海洋药物与生物制品实验室,山东青岛266237

出　　处：《中国海洋药物》2023年第2期17-22,共6页Chinese Journal of Marine Drugs

基　　金：山东省重大科技创新工程专项(2018SDKJ0402-1)资助。

摘　　要：目的为了了解水分子在尼古丁(NCT)与α4β2烟碱乙酰胆碱受体(nAChR)结合过程中的作用机制以及其在构象稳定中的作用,对NCT与α4β2 nAChR的结合进行了分子动力学(MD)模拟。方法对与激动剂NCT结合的α4β2 nAChR体系运行500 ns的全原子分子动力学模拟。结果模型表明,关键的水分子存在于α4(+)β2(-)的结合部位,形成氢键连接NCT的吡啶N、β2 L121的骨架NH原子和N109的羧基氧原子。还发现与NCT结合的α4β2 nAChR中,C环开放程度在不同亚基之间有明显的差异,结论桥接水分子通过形成3个氢键连接NCT与受体蛋白,在NCT与α4β2受体的结合中起重要作用。Objective For understanding the action of the water molecules played in the binding of nicotine toα4β2 nicotinic acetylcholine receptor(nAChR)and its role in conformational stabilization,molecule dynamics(MD)simulations were performed on theα4β2 nAChR bound with nicotine.Methods This system was investigated by one molecular dynamics simulations,with 500 ns production run performed on theα4β2 nAChR bound with nicotine.Results MD simulations of this research evidenced that this key water molecule exists at the binding site ofα4(+)β2(-),forming hydrogen bonds linking the pyridine N of nicotine,the backbone NH ofβ2 L121 and the carboxyl oxygen of N109.Evolution of the C-loop opening varied significantly between different subunits of theα4β2 nAChR,especially between theα4 andβ2 subunit for system bound with nicotine.Conclusion Bridging water molecules play an important role in the binding of nicotine toα4β2 receptors by forming three hydrogen bonds linking nicotine to the receptor.

关 键 词：水分子 NCT 烟碱乙酰胆碱受体 分子动力学模拟 

分 类 号：R914[医药卫生—药物化学]