Acta Chimica Sinica ›› 2005, Vol. 63 ›› Issue (15): 1409-1414. Previous Articles     Next Articles

Original Articles



  1. (山西大学分子科学研究所 化学生物学与分子工程教育部重点实验室 太原 030006)
  • 收稿日期:2004-05-11 修回日期:2005-04-02 出版日期:2005-08-15 发布日期:2010-12-10
  • 通讯作者: 杨频

A Practical Method for Ranking Inhibitory Activity of Huprine X Derivatives on Acetylcholinesterase via Binding Free Energy Calculations

HAN Da-Xiong, YANG Pin*   

  1. (Institute of Molecular Science, Shanxi University, Key Laboratory of Chembiolody and Molecular Engineering of the Ministry of Education, Taiyuan 030006)
  • Received:2004-05-11 Revised:2005-04-02 Online:2005-08-15 Published:2010-12-10
  • Contact: YANG Pin

In order to design novel tacrine-huperzine A hybrid (Huperzine X) derivatives, a new practical proposal was built to calculate binding free energy. The method assumed that the free energy of binding was cast simply as a linear combination of three descriptors: interaction energy between inhibitors and protein, the difference in the absolute conformation free energy of protein between the bound and unbound states, and the free energy increase of inhibitors from the stabilized conformation to activity conformation. For the total of 14 huperzine X derivatives, the result obtained from the method was found to correlate well to the inhibitory activity IC50 for acetylocholinesterases with the Spearman's correlation coefficient rs=0.85.

Key words: binding free energy, huperzine X, acetylocholinesterase, molecular dynamics