In silico prediction and structural characterization of multifunctional bioactive peptides released from olive...

Olive (Olea europaea L.) byproducts, such as seeds and leaves, are abundant agro-industrial residues and represent underexplored protein sources with potential health relevance. However, the repertoire of bioactive peptides that may be released from olive proteins during gastrointestinal digestion remains poorly characterized. This study aimed to perform a comprehensive in silico screening to identify and characterize multifunctional bioactive peptides potentially released from olive proteins during gastrointestinal digestion.

Five UniProt-reviewed Olea europaea L. proteins (annotation score 5/5) were selected as curated reference sequences and subjected to simulated gastrointestinal digestion using pepsin, trypsin, and chymotrypsin. The resulting peptides were filtered and evaluated using a battery of in silico tools to predict physicochemical properties, bioactivity, and bioavailability-related features. Molecular docking analyses were conducted to explore peptide-target interaction patterns.

Simulated digestion generated a diverse peptide pool, from which a reduced set of high-ranking candidates was prioritized based on predicted bioactivity. Correlation analyses suggested that structural features such as amphipathicity and steric accessibility were associated with stronger predicted activities. Molecular docking analyses indicated stable and target-specific interaction patterns with proteins involved in cardiometabolic and inflammatory pathways, supporting the prioritization of selected peptide candidates interacting with angiotensin-converting enzyme, dipeptidyl peptidase IV, and the TLR4/MD2 complex.

This study provides an integrated in silico screening and prioritization framework to identify olive-derived peptide candidates with predicted multifunctional bioactivity. The findings offer a rational basis to guide future experimental validation and support the valorization of olive byproducts as sources of functional food ingredients. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.