Unveiling the Potential Bioactive Peptides Derived From Goat Casein Hydrolysates Based on In Silico Analyses

ABSTRACT Bioactive peptides (BAPs) have attracted considerable interest in scientific research due to their heterogeneity in sequence and structure, which underpins various biological functionalities. In this context, goat casein, an abundant by‐product of the dairy industry, emerges as a valuable source of BAPs. The present study undertook a meticulous evaluation of the bioactive potentials of goat casein‐derived peptides through an integrated approach combining computational simulations, high‐throughput screening, and molecular docking techniques. The initial phase involved the enzymatic digestion of goat milk casein using trypsin, followed by the identification of peptides via liquid chromatography–tandem mass spectrometry (LC–MS/MS), uncovering a total of 597 peptides. Subsequent prioritization using the PeptideRanker algorithm identified 70 peptides exhibiting potential bioactivity, as denoted by scores above 0.8. Advanced screening employing the BIOPEP database and the AutoDock and CAMPR4 tools facilitated the elucidation of 16 antioxidant, 59 hypotensive, 63 hypoglycemic, 70 hypolipidemic, and 25 antimicrobial peptides. Molecular docking studies further elucidated the spontaneous nature of the interactions between the peptides and their respective receptors, predominantly mediated by hydrogen bonding and hydrophobic interactions. Four peptides specifying all activities simultaneously were synthesized, and their activities were verified by in vitro experiments. These results not only highlight an effective strategy for the high‐throughput screening of goat casein‐derived peptides but also underscore the potential of utilizing casein as a viable source of functional food ingredients. This study thereby contributes significantly to the expanding field of functional food research, suggesting a sustainable approach to explore the potential of dairy by‐products.