摘要
目的采用分子对接技术虚拟筛选苦参黄酮类化合物中葡萄糖转运蛋白4(GLUT4)转运蛋白激动剂。方法搜集现已分离鉴定的128个苦参黄酮类化合物组成配体数据库,检索RCSB PDB数据库中葡萄糖转运蛋白4蛋白晶体结构并确定本研究用优势构象,以蛋白优势结构对应DrugBank中已上市的小分子药物平均打分为阈值,应用Discovery Studio 2.5(DS2.5)软件的CDOCKER模块进行分子对接。结果虚拟筛选出打分高于阈值且排名前10%的化合物共12个并归纳了苦参黄酮作用靶点的主要活性位点,初步揭示了苦参黄酮抗糖尿病的作用机制。结论基于分子对接的虚拟筛选可推断苦参黄酮化合物中促进葡萄糖转运蛋白4转运蛋白激动的有效成分,为进一步构效关系研究及研发基于新靶点的抗糖尿病类药物提供了一定的参考。
Objective To investigate GLUT4 agonist in flavonoids of Sophora flavescens by virtual screening. Methods The database of 128 flavonoids from Sophora flavescens compound ligands was collected and the crystal structure of GLUT4 protein in the RCSB PDB database was searched and determined.In addition,the small-molecule approved drugs of targets from Drug Bank database were set as a reference with minimum score as threshold,and the CDOCKER module of Discovery Studio 2.5（ DS2.5） software was used for molecular docking.Results The scores of top 10% of total 12 compounds were screened out and the mechanism of flavonoids anti-diabetes was preliminarily revealed.Conclusion Virtual screening based on molecular docking can be used to infer the active ingredients of the flavonoids of Sophora flavescens that promote the activation of GLUT4 transporters,and providing a certain reference for further structure-activity relationship studies and the development of antidiabetic drugs based on new targets.
作者
黄佩南
于雅楠
黄晓斌
李晓芝
陈锡欣
刘怡
陈磊
王淑美
HUANG Peinan;YU Yanan;HUANG Xiaobin;LI Xiaozhi;CHEN Xixin;LIU Yi;CHEN Lei;WANG Shumei(School of Traditional Chinese Medicine,Guangdong Pharmaceutical University,Guangzhou 510006,China;School of Chinese Medicine,Southern Medical University,Guangzhou 510515,China;Key Laboratory of Traditional Chinese Medicine Digitalization Quality Evaluation under State Administration of Traditional Chinese Medicine,Guangzhou 510006,China;Guangdong Research Center for Traditional Chinese Medicine Quality,Guangzhou 510006,China)
出处
《药学研究》
CAS
2018年第5期249-252,290,共5页
Journal of Pharmaceutical Research
基金
国家级大学生创新创业训练计划项目(No.201610573010)
国家自然科学基金项目(No.81403063
81673556)
广东省基础与应用基础研究专项资金(省自然科学基金资助)项目(No.2017A030313753)
关键词
苦参黄酮
糖尿病
分子对接
葡萄糖转运蛋白4
Flavonoids from Sophora flavescens
Diabetes mellitus
Molecular docking
GLUT4
