基于中草药活性成分的GSK-3β抑制剂的分子模拟  

Molecular Simulation of GSK-3β Inhibitors Based on Active Components of Chinese Herbal Medicines

作　　者：唐文强 张静晓[3] 张丽雷[3] TANG Wen-qiang;ZHANG Jing-xiao;ZHANG Li-lei(School of Pharmacy,Shanxi Institute of International Trade & Commerce,Xi’an 712046 ,China;College of Chemistry and Environmental Engineering,Hubei University for Nationalities,Enshi 445000 ,China;Co-Innovation Center of Shanxi Green Manufacturing Technology of Traditional Chinese Medicine,Xi’an 712046 ,China)

机构地区：[1]陕西国际商贸学院医药学院,西安712046 [2]陕西省中药绿色制造技术协同创新中心,西安712046 [3]湖北民族学院化学与环境工程学院,恩施471934

出　　处：《天然产物研究与开发》2018年第12期2070-2076,共7页Natural Product Research and Development

基　　金：湖北省教育厅科学研究计划(B2017099);陕西省高校科协青年人才托举计划(20180312)

摘　　要：使用分子对接和分子动力学方法,研究了一类中草药活性成分抑制糖原合成酶激酶-3β(GSK-3β)的机理。结果表明:筛选出的芦丁、杨酶酮、二氢丹参酮I和人参皂苷Rb1能够与GSK-3β良好地结合,其中芦丁、杨酶酮和二氢丹参酮I主要结合于GSK-3β的ATP结合口袋区域,人参皂苷Rb1主要结合于GSK-3β的T-loop区域,配体和蛋白之间形成的氢键的数目和存活率是影响结合能力的主要因素,氢键的形成主要取决于配体中的含氧和含氮基团。基于这些有效成分进行结构设计可能获得GSK-3β的高效抑制剂。Molecular docking and dynamic methods were employed to explore the inhibition mechanism of several constituents from herbal medicines with Glycogen synthase kinase-3β(GSK-3β).The results showed that four selected constituents,which included rutin,myricanone,dihydrotanshinone I and ginsenoside Rb1,fitted well within the binding cleft of GSK-3β.Among them,rutin,myricanone and dihydrotanshinone I mainly binded to the ATP-binding pocket region of GSK-3β,and ginsenoside Rb1mainly binded to the T-loop region of GSK-3β.The number and the survival rate of hydrogen bonds are the main factors affecting the binding ability.The formation of hydrogen bonds mainly depends on the oxygen-containing and nitrogen-containing groups in these ligands.Structural design based on these active ingredients may result in a highly effective inhibitor of GSK-3β.

关 键 词：糖原合成酶激酶-3抑制剂 中药活性成分 分子对接 分子模拟 

分 类 号：R28[医药卫生—中药学] Q966[医药卫生—中医学]