物理化学学报 >> 2010, Vol. 26 >> Issue (03): 775-783.doi: 10.3866/PKU.WHXB20100320

生物物理化学 上一篇    下一篇

精制透骨消痛颗粒防治骨性关节炎的计算机药理学

郑春松, 徐筱杰, 刘献祥, 叶蕻芝   

  1. 福建中医学院中西医结合研究院, 福州 350108; 北京大学化学与分子工程学院, 北京 100871
  • 收稿日期:2009-11-02 修回日期:2009-12-25 发布日期:2010-03-03
  • 通讯作者: 徐筱杰, 刘献祥 E-mail:xiaojxu@pku.edu.cn; liuxianxiang@163.com

Computational Pharmacology of Jingzhi Tougu Xiaotong Granule in Preventing and Treating Osteoarthritis

ZHENG Chun-Song, XU Xiao-Jie, LIU Xian-Xiang, YE Hong-Zhi   

  1. Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou 350108, P. R. China; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China
  • Received:2009-11-02 Revised:2009-12-25 Published:2010-03-03
  • Contact: XU Xiao-Jie, LIU Xian-Xiang E-mail:xiaojxu@pku.edu.cn; liuxianxiang@163.com

摘要:

采用分子相似性分析、化学空间、分子对接、生物网络技术和药代动力学性质预测等计算机药理学方法研究中药精制透骨消痛颗粒中514个化合物的药理学机制. 结果表明: 该复方所含化合物在化学结构上具有多样性及大部分化合物在化学空间上具有类药性质; 通过514 与35个骨性关节炎疾病相关的公认靶标的相互作用及它们在靶空间的分布上阐明了精制透骨消痛颗粒防治骨性关节炎的可能作用机理, 发现了一些潜在的活性分子; 通过分析药物库中骨性关节炎的药物-靶点的作用网络及精制透骨消痛颗粒中分子-靶点的作用网络的异质性值、特征路径长度等特征, 揭示精制透骨消痛颗粒的多药物、多靶点、多途径分子作用机制. 结果有助于理解中药精制透骨消痛颗粒的复杂作用机制.

关键词: 分子对接, 化学空间, 靶空间, 骨性关节炎, 计算药理学

Abstract:

The pharmacological mechanism of 514 compounds contained in a Chinese medicine, Jingzhi Tougu Xiaotong Granule (JZTGXTG) was studied by computational pharmacological methods including analysis of molecular similarity, chemical space, molecular docking, network technology, and the predictions of absorption, distribution, metabolism, excretion and toxicity (ADME/T). Results show that compounds in JZTGXTG have the diverse structural properties and most of these compounds have good drug-like properties in their chemical spaces. The possible action mechanism is illuminated and potential active-molecules of JZTGXTG are found by studying the interactions between 514 compounds of JZTGXTG and 35 drug targets related to osteoarthritis disease and the distribution of 514 compounds in drug-target space. By analyzing network parameters of JZTGXTG compound-target interaction network and drug-target interaction network including network heterogeneity and characteristic path length, the results reveal the molecular mechanism of multi-drugs, multi-targets, and multi-pathways in JZTGXTG. The results are helpful for understanding the complicated mechanismof JZTGXTG.

Key words: Molecular docking, Chemical space, Target space, Osteoarthritis, Computational pharmacology

MSC2000: 

  • O641