物理化学学报 >> 2008, Vol. 24 >> Issue (10): 1839-1844.doi: 10.3866/PKU.WHXB20081017

研究论文 上一篇    下一篇

紫杉醚与αβ微管蛋白的分子对接

徐志广; 许旋; 袁传能   

  1. 华南师范大学化学与环境学院, 广东高校电化学储能与发电技术重点实验室, 广州 510006
  • 收稿日期:2008-04-01 修回日期:2008-06-18 发布日期:2008-10-08
  • 通讯作者: 许旋 E-mail:xuxuan@scnu.edu.cn

Molecular Docking on Taxotere Binding to αβ-Tubulin

XU Zhi-Guang; XU Xuan; YUAN Chuan-Neng   

  1. Key Laboratory of Technology on Electrochemical Storage and Power Generation in Guangdong Universities, School of Chemistry and Environment, South China Normal University, Guangzhou 510006, P. R. China
  • Received:2008-04-01 Revised:2008-06-18 Published:2008-10-08
  • Contact: XU Xuan E-mail:xuxuan@scnu.edu.cn

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摘要： 采用Insight II/Affinity对紫杉醚与αβ微管蛋白进行分子对接, 共得到10个对接构象. 应用密度泛函B3LYP/6-31G 方法计算对接口袋构象的结合能, 筛选出结合能达-190.53 kJ·mol-1的最优对接构象5. 通过构象分析建立紫杉醚与受体结合的作用模型, 结果表明, 在活性口袋的底部紫杉醚与受体间的作用主要是疏水作用, 而在活性口袋的顶部两者间主要是氢键作用. 氢键作用位置可分为A和B两个作用区, 其中A区有3个氢键, 由C13侧链分别与受体的ASP26和ARG369作用形成; B区也有3个氢键, 是由紫杉醚母环上的极性基团分别与受体的THR276、ARG278和GLN282作用产生的. 紫杉醚与αβ微管蛋白间形成的6个氢键可以有效地将紫杉醚固定在活性口袋中.

关键词: 紫杉醚, αβ微管蛋白, 分子对接

Abstract: By using Insight II/Affinity, molecular docking study on taxotere binding to αβ-tubulin was performed, and then a computational approach with B3LYP/6-31G was used to study the interactions of taxotere with αβ-tubulin. Optimum conformation 5 with binding energy of -190.53 kJ·mol-1 was obtained from ten conformations which were produced in the molecular docking process. The conformation 5 provides an interaction model for the binding of taxotere to αβ-tubulin, which shows herein both the hydrophobic and hydrogen bond interactions in the active site. The hydrophobic groups of tubulin are present in the bottomof active site, and forma hydrophobic space with the phenyl in both C13 side chain and C2—OBz group of taxotere. Six hydrogen bond interactions are found in the interaction model, which are located A and B binding sites respectively. Three hydrogen bond interactions between polarity group in C13 side chain and ASP26 and ARG369 in β-tubulin are found in the A site, and the other three hydrogen bond interactions between the polarity group in the cycle of taxotere and THR276, ARG278 and GLN282 in β-tubulin are found in B site. As a whole, hydrogen bond interactions in the upside of active site strengthen the interaction between taxotere and αβ-tubulin and prevent taxotere fromfalling off αβ-tubulin.

Key words: Taxotere, αβ-Tubulin, Molecular docking