化学学报 ›› 2011, Vol. 69 ›› Issue (20): 2427-2433. 上一篇    下一篇

研究论文

洋刀豆脲酶与抑制剂相互作用的分子对接和分子动力学研究

吕婧1,蒋勇军*,2,俞庆森1,2,邹建卫2   

  1. (1浙江大学化学系 杭州 310027)
    (2浙江大学宁波理工学院分子设计与营养工程市重点实验室 宁波 315104)
  • 收稿日期:2011-01-17 修回日期:2011-05-18 出版日期:2011-10-28 发布日期:2011-06-16
  • 通讯作者: 蒋勇军 E-mail:yjjiang@nit.net.cn
  • 基金资助:

    GSK3β激酶结构功能的分子模拟研究

Molecular Docking and Molecular Dynamics Simulations of Inhibitors Binding to Jack Bean Urease

Lü Jing1 Jiang Yongjun*,2 Yu Qingsen1,2 Zou Jianwei2   

  1. (1 Department of Chemistry, Zhejiang University, Hangzhou 310027)
    (2 Key Laboratory for Molecular Design and Nutrition Engineering of Ningbo City, Ningbo Institute of Technology, Zhejiang University, Ningbo 315104)
  • Received:2011-01-17 Revised:2011-05-18 Online:2011-10-28 Published:2011-06-16

通过洋刀豆脲酶抑制剂的筛选实验得到具有较好抑制活性的化合物2-乙酰基-γ-丁内酯(COM), 其半数抑制浓度在微摩尔浓度级别(IC50=375 μmol•L-l). 在此基础上, 使用分子对接和分子动力学(MD)模拟的方法研究洋刀豆脲酶与抑制剂乙酰氧肟酸(AHA)及活性化合物COM之间的相互作用. 用Gold3.0程序将两个小分子与洋刀豆脲酶的晶体结构进行对接, 对接得到的复合物模型使用Amber程序进行MD模拟研究. 模拟过程中, 脲酶结构中的双核镍离子活性中心选用non-bonded模型. 研究结果显示: AHA与洋刀豆脲酶结合时, Ni(1)和Ni(2)均为五配位|COM与洋刀豆脲酶结合时Ni(1)为五配位, Ni(2)为六配位的结合模型更加合理. 这些研究为了解洋刀豆脲酶与抑制剂之间的相互作用提供了重要的参考信息.

关键词: 洋刀豆脲酶, 分子对接, 分子动力学模拟, MM_GBSA, 镍离子

From the bioassay tests, compound 2-acetyl-γ-hydroxybutyric (COM) showed good inhibitory activity against Jack bean urease with IC50=375 μmol•L-l. Then the molecular docking and molecular dynamics (MD) simulations were performed to investigate the interactions between Jack bean urease and inhibitor aceto hydroxamic acid (AHA) and COM. GOLD3.0 program was used to perform the docking, and Amber was used to model the docking complex structures of inhibitor-Jack bean urease. Nonbonded model used for the nickel ions provided good reproduction of the active site of Jack bean urease during the MD simulations. The results confirmed that both nickel ions were pentacoordinated in AHA-Jack bean urease model. The binding model of the COM-Jack bean urease showed that Ni(1) was pentacoordinated while Ni(2) was hexacoordinated. The models provided useful information for understanding of the interactions between inhibitors and the protein.

Key words: Jack bean urease, molecular docking, molecular dynamics simulation, MM_GBSA, Nickel ion