基于生信分析和动力学模拟探究淡豆豉防治阿尔茨海默病的物质基础与作用机制

Exploring the material basis and mechanism of action of tempeh against Alzheimer's disease based on bioconfidence analysis and kinetic simulation

目的利用生信分析和动力学模拟方法,探究淡豆豉防治阿尔茨海默病(AD)的物质基础与作用机制。方法采用基因表达综合(GEO)数据库筛选AD原始数据集,利用GEO2R和Venny在线工具分析差异基因,绘制火山图、韦恩图。采用Metascape数据库完成交集差异基因的基因本体论(GO)分析和京都基因与基因组百科全书(KEGG)通路分析,利用String数据库对交集差异基因进行蛋白相互作用(PPI)分析。通过成份数据库搜集淡豆豉化学成份,利用Discovery Studio对符合类药性筛选条件的成份与关键(Hub)基因进行分子对接和分子动力学模拟,并分析最佳对接组合的分子间相互作用模式和作用能曲线。结果GEO数据库筛选获得3个AD原始数据集,得到22个共有差异表达基因(DEGs),Metascape数据库显示,上述DEGs除了参与神经元细胞体、神经元投射终点等生物进程外,还与神经活性配体与受体通路等多条机制通路有关。String数据库分析获得度值靠前的SYT1和GFAP作为Hub基因靶点。通过数据库收集、ADMET筛选后,得到淡豆豉中apigenin等11个符合筛选条件的化合物。通过对二维平面图分析发现,apigenin与GFAP主要通过氢键、π-烷基结合于靶蛋白的活性作用口袋,结合分子动力学模拟结果,范德华力ΔEvdw发挥主要作用,静电相互作用发挥补充作用。结论淡豆豉中的apigenin等11种成份通过氢键作用、疏水相互作用、范德华力以及静电相互作用,与神经活性配体和受体通路、GABA能突触信号通路上的靶点产生作用,进而发挥治疗AD的功效。

Objective To investigate the material basis and mechanism of action of tempeh against Alzheimer's disease(AD)using raw letter analysis and kinetic simulation methods.Methods The GEO database was used to screen the original AD dataset,and GEO2R and Venny online tools were used to analyze the differential genes and draw volcano and Wayne diagrams.Metascape database was used to complete GO analysis and KEGG signaling pathway analysis of the intersecting differential genes,and protein-protein interaction(PPI)analysis of the intersecting differential genes was performed using String database.The chemical constituents of tempeh were collected through the ingredient database,and the molecular docking and molecular dynamics simulations of the constituents and key genes that met the conditions for drug-like screening were performed using Discovery Studio,and the intermolecular interaction patterns and action energy curves of the optimal docking combinations were analyzed.Results Three AD datasets were obtained through GEO database screening,and 22 common differentially expressed genes(DEGs)were obtained.The Metascape database showed that the DEGs were not only involved in biological processes such as neuronal cell bodies and neuronal projection endpoints,but also related to multiple mechanistic pathways such as neuroactive ligand and receptor pathways.The String database analysis yielded the top-ranked SYT1 and GFAP as key gene targets.After database collection and ADMET screening,11 compounds in tempeh met the screening criteria,including apigenin from tempeh.By analyzing the 2D planar maps,it was found that the molecule-to-protein interaction was mainly through hydrogen bonding,π-alkyl binding to the active interaction pocket of the target proteins,and combined with the results of molecular dynamics simulations,the van der Waals forceΔEvdw played a major role,and electrostatic interactions played a complementary role.Conclusion Apigenin and 11 other components in tempeh interact with targets in the neuroactive ligand-receptor pathway and GABAergic synaptic signaling pathway through hydrogen bonding,hydrophobic interactions,van der Waals forces,and electrostatic interactions,thus exerting their therapeutic effects in the treatment of AD.