刘璐,赵紫彤,初鑫,等.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[J].中国海洋药物,2023,42(2):17-22.
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
投稿时间:2022-02-21  修订日期:2022-03-25
DOI:
中文关键词:  水分子  尼古丁  烟碱乙酰胆碱受体  分子动力学模拟
English Keywords:water molecule  nicotine  nicotinic acetylcholine receptor  molecular dynamics simulation
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作者单位E-mail
刘璐 中国海洋大学 17854172001@163.com 
赵紫彤 中国海洋大学 1063860770@qq.com 
初鑫 中国海洋大学 366579597@qq.com 
于日磊* 中国海洋大学 ryu@ouc.edu.com 
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中文摘要:
      目的 为了了解水分子在尼古丁与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,本研究对尼古丁与α4β2 nAChR的结合进行了分子动力学(MD)模拟。方法 对与激动剂尼古丁结合的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,形成氢键连接尼古丁的吡啶N、β2 L121的骨架NH原子和N109的羧基氧原子。还发现与尼古丁结合的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个氢键连接尼古丁与受体蛋白,在尼古丁与α4β2受体的结合中起重要作用。
English Summary:
      Objective For understanding the action of the water molecules played in the binding of nicotine to α4β2 nicotinic acetylcholine receptor (nAChR) and its role in conformational stabilization, molecule dynamics (MD) simulations were performed on the α4β2 nAChR bound with nicotine. Methods This system was investigated by one molecular dynamics simulations, with 500 ns production run performed on the α4β2 nAChR bound with nicotine. Results MD simulations of this research evidenced that this key water molecule exists at the binding site of α4(+)β2(-), forming hydrogen bonds linking the pyridine N of nicotine, the backbone NH of β2 L121 and the carboxyl oxygen of N109. Evolution of the C-loop opening varied significantly between different subunits of the α4β2 nAChR, especially between the α4 and β2 subunit for system bound with nicotine. Conclusion Bridging water molecules play an important role in the binding of nicotine to α4β2 receptors by forming three hydrogen bonds linking nicotine to the receptor.
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