In Silico Structure-Based Multi-Targeted Molecular Docking Analysis of Ginkgo Biloba Phytocompounds Against Alzheimer’s Disease Associated Proteins

Alzheimer disease (AD) is a multi-factorial neurodegenerative disease that is characterized by accumulation of amyloid-beta (Aβ), protein aggregation and progressive neuronal dysfunction. Some of the key proteins that are involved in the molecular pathways of AD include amyloid precursor protein (APP), neprilysin (NEP) and alpha-synuclein (SNCA). In the current study, the selected phytochemicals of Ginkgo biloba: amentoflavone, proanthocyanidin, quercetin, sciadopitysin and stigmasterol were tested using molecular docking to explore their in-silico binding characteristics with these targets. The structure of the proteins in 3D was retrieved in the Protein Data Bank and was ready to undergo docking. AutoDock Vina was used to perform molecular docking and analyze protein-ligand interactions with Discovery Studio Visualizer. In the case of APP, the docking region was defined at the β-secretase cleavage-proximal region of the ectodomain, which is structurally relevant. It should be mentioned that APP is a substrate protein and does not have a catalytic active site. NEP and SNCA docking was done at their respective functional sites. The findings reveal that the selected phytochemicals demonstrate good binding interactions with the target proteins, with amentoflavone having a relatively high binding affinity to APP. Analysis of interaction showed that hydrogen bonding and hydrophobic contacts were found in the specified binding areas. Such conclusions are founded entirely on a computational analysis and are to be viewed as hypothesis-generating. The experiment does not determine biological activity or Computational potential. The interactions need to be further experimentally validated by in vitro and in vivo studies to determine the functional relevance of these interactions.