物理化学学报 >> 2012, Vol. 28 >> Issue (05): 1257-1264.doi: 10.3866/PKU.WHXB201202212

生物物理化学 上一篇    下一篇

复方心可舒治疗冠心病多靶点作用的分子对接

胡衍保1, 彭静波1, 顾硕2, 裴剑锋2, 邹忠梅1   

  1. 1. 中国医学科学院北京协和医学院药用植物研究所, 北京 100193;
    2. 北京大学理论生物学中心, 北京 100871
  • 收稿日期:2011-11-22 修回日期:2012-02-07 发布日期:2012-04-26
  • 通讯作者: 裴剑锋, 邹忠梅 E-mail:zmzou@implad.ac.cn; jfpei@pku.edu.cn
  • 基金资助:

    国家自然科学基金(81073021)和“重大新药创制”科技重大专项(2009ZX09501-002, 2012ZX09301002-001)资助项目

Molecular Docking in Xin-Ke-Shu Preparation's Multi-Target Effect on Coronary Heart Disease

HU Yan-Bao1, PENG Jing-Bo1, GU Shuo2, PEI Jian-Feng2, ZOU Zhong-Mei1   

  1. 1. Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100193, P. R. China;
    2. Center for Theoretical Biology, Peking University, Beijing 100871, P. R. China
  • Received:2011-11-22 Revised:2012-02-07 Published:2012-04-26
  • Contact: PEI Jian-Feng, ZOU Zhong-Mei E-mail:zmzou@implad.ac.cn; jfpei@pku.edu.cn
  • Supported by:

    The project was supported by the National Natural Science Foundation of China (81073021) and“Innovative Drug Development”Key Project of the Ministry of Science and Technology of China (2009ZX09501-002, 2012ZX09301002-001).

摘要: 心可舒为治疗冠心病的常用中药复方, 临床疗效确切, 但是其效应物质基础和作用机制一直没有得到明确的解释. 本文以从心可舒中直接鉴定出的51 个化学成分和过氧化物酶体增生物激活受体γ (PPAR-γ), 血管紧张素I 转化酶(ACE), 羟甲基戊二酰辅酶A还原酶(HMGR), 环氧合酶2 (COX-2)以及凝血酶(thrombin)等5个冠心病相关靶点为研究对象, 采用LibDock 和AutoDock 2种分子对接程序联合对接的方法对以上化学成分和靶点的相互作用进行探讨. 首先用均方根偏差(RMSD)和富集因子(EF)考察了2种程序对于5个靶点受体配体结合体系的适用性, 进而发现当2 种程序联合使用时, 各靶点的富集因子较程序单独使用时有明显的提高,因而最终使用LibDock 和AutoDock 联合进行筛选. 计算结果表明心可舒中的葛根苷A、葛根苷B、丹酚酸A和丹酚酸C 4 个化合物可能作用于2 个或者2 个以上的靶点, 另外还有8 个化合物能够分别作用于5 个靶点的其中1个靶点. 本研究初步阐释了心可舒多靶点作用的分子机制, 为心可舒的后期开发提供了一定的参考.

关键词: 分子对接, 心可舒, 中药复方, 冠心病, 多靶点作用, 富集因子

Abstract: Xin-Ke-Shu (XKS), a traditional Chinese medicine (TCM) preparation, has been widely used for treatment of coronary heart disease (CHD) in China. However, the active constituents of XKS and their interactions with targets remain unclear. In this study, we assessed two docking programs, LibDock and AutoDock, by calculating the root-mean-square deviation (RMSD) of X-ray structure reproduction and the enrichment factor (EF) in virtual screening; both proved to be practical in our protein-ligand complex systems. Moreover, the combined use of the two programs yielded better EFs for each target. We therefore used a combination of the two programs to investigate the interactions of the 51 chemical constituents identified from XKS with five CHD targets, namely peroxisome proliferator activated receptor γ (PPAR-γ), angiotensin-converting enzyme (ACE), hydroxymethylglutaryl coenzyme A receptor (HMGR), cyclooxygenase-2 (COX2), and thrombin. The docking results suggest that pueroside A, pueroside B, salvianolic acid A, and salvianolic acid C can interact with two or more targets, and the other eight compounds may be potent for at least one of the five targets. In this research, we propose a strategy for studying TCM preparations, and suggest that XKS has a multi-target effect on CHD.

Key words: Docking, Xin-Ke-Shu, Traditional Chinese medicine, Coronary heart disease, Multi-target effect, Enrichment factor

MSC2000: 

  • O641