物理化学学报 >> 2009, Vol. 25 >> Issue (03): 417-422.doi: 10.3866/PKU.WHXB20090304

研究论文 上一篇    下一篇

人类丝氨酸消旋酶的同源模建及其与多肽类抑制剂的分子对接

赵勇山 郑清川 张红星 楚慧郢 孙家钟   

  1. 吉林大学理论化学研究所, 理论化学计算国家重点实验室, 长春 130023
  • 收稿日期:2008-11-04 修回日期:2008-12-11 发布日期:2009-03-02
  • 通讯作者: 郑清川 E-mail:zhengqch@jlu.edu.cn

Homology Modeling of Human Serine Racemase and Its Molecular Docking with Peptide Inhibitors

ZHAO Yong-Shan, ZHENG Qing-Chuan, ZHANG Hong-Xing, CHU Hui-Ying, SUN Chia-Chung   

  1. State Key Laboratory of Theoretical and Computational Chemistry, Institute of Theoretical Chemistry, Jilin University, Changchun 130023, P. R. China
  • Received:2008-11-04 Revised:2008-12-11 Published:2009-03-02
  • Contact: ZHENG Qing-Chuan E-mail:zhengqch@jlu.edu.cn

摘要:

利用同源模建和分子动力学模拟方法构建了人类丝氨酸消旋酶(hSR)的三维结构, 并利用profile-3D和procheck方法评估了模型的可靠性. 在此基础上用分子对接程序(affinity)将多肽类抑制剂A和B分别与hSR进行对接, 获得了其复合物结构的理论模型. 通过配体与受体之间相互作用能和结构分析给出了此类抑制剂与hSR的具体结合方式, 明确了hSR与此类抑制剂结合时起重要作用的氨基酸残基, 为基于人类丝氨酸消旋酶三维结构的药物设计提供重要的参考信息.

关键词: 人类丝氨酸消旋酶, 分子动力学模拟, 分子对接, 同源模建

Abstract:

The three dimensional structure of human serine racemase (hSR) was modeled and refined using homology modeling and molecular dynamics simulation. This model was assessed by profile-3D and procheck, which confirmed that the refined model was reliable. Complex structures of peptide inhibitors with hSR were obtained and investigated through ligand-receptor docking studies by a molecular docking program, affinity. The binding pattern predicted by the affinity module revealed that important residues interacted with the peptide inhibitors and the module provided further refinement of the hSR/inhibitor binding interaction that may be used as a basis for new structure-based design efforts.

Key words: Human serine racemase, Molecular dynamics simulation, Molecular docking, Homology modeling

MSC2000: 

  • O641