Identifying repurposed drugs as potential inhibitors of Apolipoprotein E: A bioinformatics approach to target complex diseases associated with lipid metabolism and neurodegeneration

Apolipoprotein E (ApoE), a pivotal contributor to lipid metabolism and neurodegenerative disorders, emerges as an attractive target for therapeutic intervention. Within this study, we deployed an integrated in-silico strategy, harnessing structure-based virtual screening, to identify potential compounds from DrugBank database. Employing molecular docking, we unveil initial hits by evaluating their binding efficiency with ApoE. This first tier of screening narrows our focus to compounds that exhibit a strong propensity to bind with ApoE. Further, a detailed interaction analysis was carried out to explore the binding patterns of the selected hits towards the ApoE binding site. The selected compounds were then evaluated for the biological properties in PASS analysis, which showed anti-neurodegenerative properties. Building upon this foundation, we delve deeper, employing all-atom molecular dynamics (MD) simulations extending over an extensive 500 ns. In particular, Ergotamine and Dihydroergocristine emerge as noteworthy candidates, binding to ApoE in a competitive mode. This intriguing binding behavior positions these compounds as potential candidates warranting further analysis in the pursuit of novel therapeutics targeting complex diseases associated with lipid metabolism and neurodegeneration. This approach holds the promise of catalyzing advancements in therapeutic intervention for complex disorders, thereby reporting a meaningful pace towards improved healthcare outcomes.