卢文丹,李莉,申艳佳,周睿,杨冉,庞晓丛,杜冠华
LU Wen-dan,LI Li,SHEN Yan-jia,ZHOU Rui,YANG Ran,PANG Xiao-cong,DU Guan-hua

• 1:中国医学科学院北京协和医学院药物研究所药物靶点研究与新药筛选北京市重点实验室
• 2:昆明医科大学生物医学工程研究中心

摘要(Abstract)：

该研究采用分子对接和网络药理学等生物信息学方法,构建中药经典复方小续命汤"成分-血管舒缩G蛋白偶联受体(GPCR)靶点"网络,研究复方小续命汤调控血管舒缩功能的有效成分及潜在靶点。通过"国家人口与健康科学数据共享平台药学数据中心"提供的"中国天然产物化学成分库"、TCMSP数据库及文献检索收集复方小续命汤12味中草药所含的化学成分,经过类药性和代谢性质等的预测与筛选后,建立分子库。利用RCSB Protein Data Bank数据库和Discovery Studio 4.1内置建模工具获得与血管舒缩相关的5类GPCR:5-羟色胺1A及1B受体(5-HT1AR,5-HT1BR)、血管紧张素Ⅱ1型受体(AT1R)、β2肾上腺素能受体(β2-AR)、尾加压素Ⅱ受体(hUTR)和内皮素受体B(ETB)及相关活性位点。将分子库与靶点进行Libdock分子对接,取每个靶点评分最高的50个化合物进行统计。收集到的数据通过Cytoscape 3.4.0进行化学成分和靶点的网络建模和分析。结果表明,复方小续命汤大多数化学成分作用于不同的血管舒缩相关GPCR靶点,少数有效成分可同时作用于多个GPCR靶点,并形成协同效应达到舒张血管的效果。
In this study, bioinformatics methods such as molecular docking and network pharmacology were adopted to establish Xiaoxuming Decoction(XXMD) "compound-vasodilatory and vasoconstrictory related G protein-coupled receptors(GPCR) targets" network, then the vascular function regulatory effective components and the potential targets of XXMD were analyzed. Based on the XXMD herb sources, the chemical structures of the compounds were retrieved from the national scientific data sharing platform for population and health pharmaceutical information center, TCMSP database and the latest research literatures. The chemical molecular library was established after class prediction and screening for medicinal and metabolic properties. Then, five kinds of vasodilatory and vasoconstrictory related GPCR crystal structure including 5-HT receptors(5-HT1 AR, 5-HT1 BR), AT1 R, β2-AR, hUTR and ETB were retrieved from RCSB Protein Data Bank database or constructed by homology modeling of Discovery Studio 4.1 built-in modeling tools. After virtual screening by Libdock molecular docking, the highest rated 50 compounds of each target were collected and analyzed. The collected data were further used to construct and analyze the network by Cytoscape 3.4.0.The results showed that most of the chemical composition effects were associated with different vasodilatory and vasoconstrictory related GPCR targets, while a few effective components could be applied to multiple GPCR targets at the same time, therefore forming synergies and vasorelaxant effects of XXMD.

关键词(KeyWords)： 网络药理学;小续命汤;G蛋白偶联受体;分子对接
network pharmacology;Xiaoxuming Decoction;G protein-coupled receptors;molecular docking

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2013ZX09508104,2013ZX09402203);; 国家自然科学基金项目(81102444,81473383);; 中国医学科学院医学与健康科技创新工程项目(2016-I2M-3-007)

作者(Author): 卢文丹,李莉,申艳佳,周睿,杨冉,庞晓丛,杜冠华
LU Wen-dan,LI Li,SHEN Yan-jia,ZHOU Rui,YANG Ran,PANG Xiao-cong,DU Guan-hua

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