论文部分内容阅读
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。
OBJECTIVE: To screen the inhibitory components of HMG-CoA reductase in Fufang Danshen Prescription by Autodock program and to explore the application of virtual screening method based on molecular docking in the study of traditional Chinese medicine. METHODS: A compound library of compound Salvia miltiorrhiza compound containing natural and metabolic components was constructed. Molecules with 5, 11, 11, and 11 rotations were randomly selected to be docked with HMG-CoA reductase to investigate the Autodock parameters. In addition, we randomly selected 10 molecules of HMG-CoA reductase inhibitors known from IC50 from the MDDR2007 database to investigate the accuracy of Autodock docking results. Results: According to the results of the parameter examination, the molecular structure of the compound library was divided into two parts by using eight rotatable keys as the boundary. Different docking parameters were set and the natural and metabolic compound libraries of compound Salvia miltiorrhiza were screened to improve the efficiency of Autodock virtual screening , And four potential inhibitory components of IC50 at 102 nmol.L -1 were obtained. The accuracy of the results showed that the correlation coefficient R2 between the experimental value and the predicted value of the positive inhibitor was 0.865, which proves that Autodock can carry out HMG-CoA reductase Inhibitor screening research is more reliable. CONCLUSIONS: Studies have shown that Fufang Danshen Prescription contains potential HMG-CoA reductase inhibitory components. This study lays the foundation for the research on the material basis of traditional Chinese medicine and prescription based on virtual docking method based on molecular docking.