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化学学报
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化学学报 ›› 2005, Vol. 63 ›› Issue (5): 434-438. 上一篇    

研究简报

基于HPPK靶标酶的分子对接研究——金属离子Mg2＋的影响

赵文娜，邹建卫*，蒋勇军，马国正，俞庆森   

  1. (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 315100)
  • 投稿日期:2004-06-14 修回日期:2004-11-08 发布日期:2010-12-10
  • 通讯作者: 邹建卫

Influence of Magnesium Ion on Molecular Docking Based on HPPK

ZHAO Wen-Na, ZOU Jian-Wei*, JIANG Yong-Jun, MA Guo-Zheng, YU Qing-Sen   

  1. (Key Laboratory for Molecular Design and Nutrition Engineering, Ningbo Institute of Technology,
    Zhejiang University, Ningbo 315100)
  • Received:2004-06-14 Revised:2004-11-08 Published:2010-12-10
  • Contact: ZOU Jian-Wei

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6-羟甲基-7,8-二氢喋呤磷酸化酶(HPPK)催化细菌进行叶酸合成反应中的第一步, 即焦磷酰从三磷酸酰酐(ATP)转移到6-羟甲基-7,8-二氢喋呤(HP), 被认为是基于结构虚拟筛选新型抗生素的理想靶标. 本工作分别以HPPK和含有金属离子Mg2＋的HPPK为受体, 以底物类似物为配体进行了对接, 发现活性口袋大小、金属镁离子对对接结果有较大的影响. 特别是金属镁离子的加入不仅可大大提高对接结果的可信度, 同时可增加虚拟筛选的命中率. 这一结果将为设计新的HPPK抑制剂提供一定的理论指导.

关键词: 6-羟甲基-7,8-二氢喋呤磷酸化酶(HPPK), 分子动力学, 分子对接, 金属离子影响

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyzes pyrophosphoryl transfer from adenosine triphosphate (ATP) to 6-hydroxymethyl-7,8-dihydropterin (HP), the first reaction in the folate pathway, and is thought to be an ideal target for developing novel antimicrobial agents. In the present work, molecular docking studies on the interactions of HPPK with the substrate analogues have been performed. Particularly, the effect of the intrinsic metal ion upon the docking has been examined. It has been showed that the incorporation of Mg2＋cation in the molecular docking processes plays an important role not only in obtaining reliable docking results but also in improving the hit ratio in the "in silico" drug screening. This may provide some helpful information for our designing new antimicrobial agents based on HPPK.

Key words: 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK), molecular dynamics, docking, metal ion effect