独活对巨噬细胞迁移抑制因子抑制作用的有效成分虚拟筛选研究

Study on Virtual Screening of Active Components in Angelicae Pubescentis Radix for Inhibiting MIF

目的筛选独活对巨噬细胞迁移抑制因子(MIF)抑制作用的有效成分,为独活治疗炎症和免疫介导疾病的作用机制研究及MIF抑制剂研发提供参考。方法以中国台湾中医药资料库中独活有效成分小分子化合物为对接配体库、MIF晶体结构为对接受体进行分子对接,筛选结合能高于原配体的小分子。对结合后的复合物构像进行相互作用分析,选取最佳配体小分子与大分子复合物进行10ns的动力学模拟,分析均方根偏差(RMSD)值。操作平台为Linux系统,采用OpenBabelGUI2.4.1进行小分子修饰,Pyrx0.8进行虚拟筛选,NAMD2.13进行分子动力学模拟,VMD1.9.3、Discovery studio4.5及Ligplot+1.4.5进行对接结果及动力学模拟结果分析。结果筛选出优于原配体的独活有效成分4种,分子相互作用分析提示主要作用残基8个,主要作用力为氢键及疏水作用,动力学模拟结果表明最佳配体小分子与受体结合较稳定。结论本研究提示独活抗炎作用机理可能与抑制MIF活性有关,其抑制作用有效成分主要有4种,可为研究和设计MIF抑制剂提供参考。

Objective To screen the active components of Angelicae Pubescentis Radix for inhibiting MIF;To provide references for the study on the mechanism of inflammatory and immune-mediated diseases and the development of MIF inhibitors.Methods Using the small molecule compound of the active components in the TCM database of Taiwan as a docking ligand library,the MIF crystal structure was the acceptor for molecular docking,and small molecules with higher binding energy than the original ligand were screened.The interaction analysis of the combined complex conformation was carried out,and the optimal ligand small molecule and macromolecular complex were selected for 10 ns kinetic simulation to analyze the root mean square deviation(RMSD)value.The operating platform was Linux system.OpenBabelGUI2.4.1 was used for small molecule modification,Pyrx0.8 for virtual screening,NAMD2.13 for molecular dynamics simulation,VMD1.9.3,Discovery studio4.5 and Ligplot+1.4.5 for docking results and dynamics simulation results analysis.Results Four active components were screened out,which were superior to the original ligand.Molecular interaction analysis indicated that there were 8 main action residues,and main force was hydrogen bonding and hydrophobic interaction.Kinetic simulation results showed that the binding of small molecules of the best ligand to the receptor was stable.Conclusion It is indicated that the anti-inflammatory mechanism of Angelicae Pubescentis Radix may be related to the inhibition of MIF activity.There are four main active components of Angelicae Pubescentis Radix,which can provide references for the study and design of MIF inhibitors.