基于Discovery Studio平台对TGF-β1中药小分子抑制剂的虚拟筛选  

Virtual screening of TGF-β1 inhibitors of Chinese materia medica small molecule based on Discovery Studio platform

作　　者：唐彪 王浩翔 付晓丽 黄璐 陈惠[1] 唐自钟 姚慧鹏[1] 单志[1] 王刚[2] 肖义蓉 TANG Biao;WANG Hao-xiang;FU Xiao-li;HUANG Lu;CHEN Hui;TANG Zi-zhong;YAO Hui-peng;SHAN Zhi;WANG Gang;XIAO Yi-rong(College of Life Sciences,Sichuan Agricultural University,Ya’an 625014,China;Sichuan Food Fermentation Industry Research and Design Institute,Chengdu 611130,China;Sichuan Agricultural University Hospital,Ya’an 625014,China)

机构地区：[1]四川农业大学生命科学学院,雅安625014 [2]四川省食品发酵工业研究设计院,成都611130 [3]四川农业大学校医院,雅安625014 [4]四川农业大学生命科学学院生物化学与分子生物学实验室,雅安625014

出　　处：《中华中医药杂志》2021年第11期6669-6673,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：四川省应用基础研究计划(No.2019YJ0549);四川省科学技术厅苗木工程计划(No.201958);四川省科学技术计划(No.2019YFG0154)。

摘　　要：目的:利用中药化学专业数据库与TCMSP分析平台,运用计算机辅助药物设计技术对转化生长因子-β1(TGF-β1)蛋白进行虚拟筛选,寻找潜在的中药小分子抑制剂。方法:通过Discovery Studio 2.5(DS)软件进行药效团模型的构建,应用Hypogen算法预测出潜在活性位点,并分别使用Ramanchandran Plot和Profile-3D评估模型,利用优化的模型进行对实验中药小分子库进行虚拟筛选,最后对筛选出的中药进行ADMET性质预测和分子动力学模拟。结果:应用Hypogen算法成功预测出6个潜在活性位点且模型表现良好,成功从黄芪、丹参、三七中筛选出4种与TGF-β1结合良好的天然小分子化合物,并分析了其结合模式。结论:黄芪、丹参、三七的抑癌效果很可能是通过抑制TGF-β1的激活实现的。Objective: To screen transforming growth factor-beta 1(TGF-β1) for potential small molecule inhibitors of Chinese materia medica by virtue of TCM Chemistry Database and TCMSP analysis platform and computer-aided drug design technology. Methods: The pharmacophore model was constructed by Discovery Studio 2.5(DS) software, the potential active sites were predicted by Hypogen algorithm, and the models were evaluated by Ramanchandran plot and Profile-3D respectively.The optimized model is used to conduct virtual screening of small molecule libraries of experimental Chinese medicines.Finally, ADMET property prediction and molecular dynamics simulation are carried out for the selected Chinese medicines.Results: Six potential active sites were successfully predicted by Hypogen algorithm and the model performed well. Four natural small molecule compounds with good binding to, TGF-β1 were successfully screened from astragalus membranaceus, salvia miltiorrhiza and panax notoginseng, and their binding modes were analyzed separately. Conclusion: The antitumor effect of astragalus membranaceus, salvia miltiorrhiza and panax notoginseng may be achieved by inhibiting the activation of TGF-β1.

关 键 词：转化生长因子-Β1 中药小分子抑制剂 分子对接 虚拟筛选 

分 类 号：R285[医药卫生—中药学]