Chem. J. Chinese Universities ›› 2010, Vol. 31 ›› Issue (2): 374.

• Articles • Previous Articles     Next Articles

Selective Inhibition Study of Apicidin Towards Class I HDACs by Molecular Dynamics Simulation

LI Xiao-Hui1*, ZHAO Jun-Wei1, TENG Hu1, NISHINO Norikazu2, XIU Zhi-Long1*   

  1. 1. School of Environment and Biological Science and Technology, Dalian University of Technology, Dalian 116024, China;
    2. Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan

  • Received:2009-03-17 Online:2010-02-10 Published:2010-02-10
  • Contact: XIU Zhi-Long. E-mail: zhlxiu@dlut.edu.cn; LI Xiao-Hui. E-mail: lxhxh@dlut.edu.cn
  • Supported by:

    国家“八六三”计划项目(批准号: 2007AA021604)资助.

Abstract:

The selective inhibitory activity of cyclic tetrapeptides apicidin towards class I histone deacetylases(HDACs) was studied by molecular dynamics simulation. The 3D structure of HDAC1 was constructed by homology modeling using the X-ray structure of HDAC8 as template. Furthermore, the 3500 ps molecular dynamics simulations were performed on both apicidin-HDAC1 and apicidin-HDAC8 complexes, which were obtained by molecular docking. As a result, the Arg270 locating at the entrance of the HDAC1 active pocket played a crucial role in forming stable interactions with apicidin. There were two lasting hydrogen bonds between apicidin and HDAC1 during the molecular dynamics simulation, while none between apicidin and HDAC8. This difference could be another important reason for the high inhibitory activity of apicidin to HDAC1.

Key words: Apicidin; Histone deacetylase; Molecular dynamics; Homology modeling; Molecular docking

TrendMD: