Lu Wen-Dan, Li Li, Shen Yan-Jia, Zhou Rui, Yang Ran, Pang Xiao-Cong, Du Guan-Hua
Beijing Key Laboratory of Drug Targets Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Biomedical Engineering Research Center of Kunming Medical University, Kunming 650500, China.
Zhongguo Zhong Yao Za Zhi. 2018 Dec;43(23):4698-4708. doi: 10.19540/j.cnki.cjcmm.20181009.004.
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-HT1AR, 5-HT1BR), AT1R, 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.
本研究采用分子对接、网络药理学等生物信息学方法，构建消旋明汤（XXMD）“复方-血管舒张和血管收缩相关G蛋白偶联受体（GPCR）靶点”网络，进而分析XXMD的血管功能调节有效成分及潜在靶点。基于XXMD的药材来源，从国家人口与健康药学信息中心科学数据共享平台、中药系统药理学数据库（TCMSP）及最新研究文献中检索化合物的化学结构。经药用和代谢特性分类预测及筛选后，建立化学分子库。随后，从RCSB蛋白质数据库中检索5种血管舒张和血管收缩相关GPCR晶体结构，包括5-羟色胺受体（5-HT1AR、5-HT1BR）、血管紧张素Ⅱ1型受体（AT1R）、β2肾上腺素能受体（β2-AR）、人尿嘧啶受体（hUTR）和内皮素B型受体（ETB），或利用Discovery Studio 4.1内置建模工具通过同源建模构建。经Libdock分子对接虚拟筛选后，收集并分析各靶点评分最高的50种化合物。收集的数据进一步用于通过Cytoscape 3.4.0构建和分析网络。结果表明，大部分化学成分的作用与不同的血管舒张和血管收缩相关GPCR靶点有关，少数有效成分可同时作用于多个GPCR靶点，从而形成XXMD的协同作用和血管舒张效应。
