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.docxVIP

PAGE PAGE 1 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 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讨论5304〔2021〕05-0105-04　　DOI：10.3969/j.issn.1005-5304.2021.05.022 开放科学〔资源服务〕标识码〔OSID〕：　　Abstract： 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.　　Keywords： MIF; Angelicae Pubescentis Radix; inhibitors; virtual screening; molecular dynamics simulation 2.6 ?的结构。最终确定PDB ID为1LJT的蛋白晶体结构为对接受体