Computational exploration of phycobiliproteins-derived peptides: in-silico gastrointestinal digestion and multi-target molecular docking against Alzheimer’s disease-related enzymes

Abstract

Abstract Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by amyloid-β (Aβ) accumulation, Tau hyperphosphorylation, and cholinergic dysfunction, necessitating multi-target therapeutic strategies. This study evaluated phycobiliproteins (PBPs) as dietary precursors of neuroprotective compounds acting on multiple AD pathways. After simulated gastrointestinal digestion, peptide fractions P1 (GCAPR), P2 (QAGDQL), and P3 (AGDASVL) were assessed alongside phycocyanobilin (PCB) using molecular docking against Beta-secretase 1, Glycogen synthase kinase 3 beta, Acetylcholinesterase, and Butyrylcholinesterase. PCB showed strong affinities toward BChE (–10.0 kcal/mol) and GSK-3β (–8.4 kcal/mol), suggesting modulation of tauopathic and late-stage cholinergic pathways. P2 exhibited notable binding to AChE (–8.8 kcal/mol) and BACE1 (–7.6 kcal/mol), indicating effects on amyloidogenic and early cholinergic mechanisms, while P1 and P3 provided complementary moderate activity. Overall, these findings support further investigation of PBPs as potential sources of bioactive compounds for functional food and nutraceutical applications targeting AD-related pathways.