利用Autodock筛选复方丹参方中HMG-CoA还原酶抑制活性成分(英文)  

Screening of HMG-CoA Reductase Inhibitors from Composite Salvia Miltiorrhiza Using Autodock

作　　者：盖伟[1] 张燕玲[1] 艾路[1] 乔延江[1] 

机构地区：[1]北京中医药大学中药信息工程研究中心,北京100102

出　　处：《中国天然药物》2010年第1期51-56,共6页

基　　金：supported by the Major State Basic Research Development Program of China (973 Program) (No.2005CB523401,No.2006CB504703);national special funds for scientific research on public causes (No.200707010)~~

摘　　要：目的:利用Autodock程序筛选复方丹参方中HMG-CoA还原酶抑制性成分,探讨基于分子对接的虚拟筛选方法在中药研究中的应用。方法:构建包含天然及代谢成分的复方丹参方化合物库,随机选取可旋转键数为5,8,11,14,17的分子分别与HMG-CoA还原酶对接,以考察Autodock的3个参数。此外,从MDDR2007数据库中随机选取10个IC50已知的HMG-CoA还原酶抑制剂分子进行对接,考察Autodock对接结果的准确性。结果:根据参数考察结果以8个可旋转键为界划分化合物库中的分子为两部分,分别设置不同的对接参数,对复方丹参天然及代谢化合物库进行虚拟筛选,提高了Autodock虚拟筛选的效率,得到了4个预测IC50在102nmol.L?1水平的潜在抑制成分;准确性考察结果显示阳性抑制剂分子的实验值与预测值的相关系数R2为0.865,证明利用Autodock开展HMG-CoA还原酶抑制剂筛选研究较为可靠。结论:研究表明复方丹参方中含有潜在HMG-CoA还原酶抑制性成分。为开展基于分子对接的虚拟筛选方法探讨中药及方剂的物质基础研究奠定了基础。AIM： To screen the inhibitors of HMG-CoA reductase from Composite Salvia Miltiorrhiza and explore the application of the virtual screening approach in the research of traditional Chinese medicine. METHODS： A compound collection of Composite Salvia Miltiorrhiza was built including both natural compounds and metabolic products. Before Autodock was employed to screen the collection, three important docking parameters of Autodock were investigated in order to enhance the screening efficiency. The screen- ing performance of Autodock was also evaluated by selecting and docking ten positive inhibitors whose experimental ICs0 were avail- able in MDDR database. RESULTS： A torsion-dependent strategy for docking parameter assignment was proposed based on parameter investigation, which improved the screening efficiency significantly. Performance evaluation indicated that the correlation coefficient （R2） between the predicted binding free energy and in vivo experimental ICs0 was 0.865. Four phenolic acids were found to possess both quite low binding free energy and reasonable pose inside the binding site. CONCLUSION： The Composite Salvia Miltiorrhiza contains constituents possessing potential inhibitive activity against HMG-CoA reductase. It is a feasible way to screen the traditional Chinese medicine with virtual screening approach and the screening speed can be improved by the torsion-dependent assignment strategy.

关 键 词：AUTODOCK 参数考察 HMG—CoA还原酶 分子对接 中药 

分 类 号：R965[医药卫生—药理学]