化学学报 ›› 2011, Vol. 69 ›› Issue (17): 2026-2030. 上一篇    下一篇

研究论文

雪卡毒素毒性机理的分子对接及分子动力学研究

郑杰1,赵斌1,闫鸿鹏1,张焜1,张大鹏2,赵肃清*,1   

  1. (1广东工业大学轻工化工学院 广州 510006)
    (2广州医学院 广州 510182)
  • 收稿日期:2010-12-17 修回日期:2011-04-18 出版日期:2011-09-14 发布日期:2011-05-17
  • 通讯作者: 赵肃清 E-mail:suqingzhao@yahoo.com.cn
  • 基金资助:

    国家自然科学基金;广东省自然科学基金

Molecular Docking and Molecular Dynamics Simulation Studies of Toxicity Mechanism of Ciguatoxin

Zheng Jie1 Zhao Bin1 Yan Hongpeng1 Zhang Kun1 Zhang Dapeng2 Zhao Suqing*,1   

  1. (1 Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006)
    (2 Guangzhou Medical University, Guangzhou 510182)
  • Received:2010-12-17 Revised:2011-04-18 Online:2011-09-14 Published:2011-05-17
  • Contact: Su-Qing ZHAO E-mail:suqingzhao@yahoo.com.cn

采用分子对接和分子动力学方法, 研究了雪卡毒素与其毒性作用靶点之一钠通道的结合模式, 并与钠通道阻滞剂奎尼丁比较. 研究结果表明, 雪卡毒素、奎尼丁与钠通道作用方式有所不同. 分子动力学模拟表明, 对接受体-配体复合物体系在2.5 ns的模拟过程中稳定. 奎尼丁在钠通道中央与GLU1784, THR1858各形成1个稳定氢键, 吡啶环与PHE1791有疏水相互作用. 雪卡毒素在钠通道外侧与SER1782, GLU1784, LEU1786以及GLU1788各形成1个持续存在的氢键, 从而激活钠通道产生毒性作用.

关键词: 分子对接, 分子动力学, 雪卡毒素, 钠通道, 毒性机制

Binding modes between CTX (Ciguatoxin) and sodium channel, which is one of the targets about CTX toxic effects, were simulated through molecular docking and dynamics method, compared with Quinidine. The docking results indicated that CTX and Quinidine shared different binding modes to sodium channel. The ligand-receptor complexes obtained by molecular docking are stable during 2.5 ns molecular dynamics simulation. Quinidine is tightly held to sodium channel centeral residues of GLU1784 and THR1858 with one hydrogen bond respectively. Its pyridine ring has hydrophobic interactions with residue of PHE1791, which produces the effect of sodium channel block. The binding site of CTX is far away from sodium channel center, one stable hydrogen bond interaction has been formed with residues of SER1782, GLU1784, LEU1786 and GLU1788 respectively. It may promote sodium channel opening and activate sodium channel, and produce its toxic effects.

Key words: molecular docking, molecular dynamics, ciguatoxin, sodium channel protein, mechanism of toxicity