Proteomic Characterization and Molecular Mechanism of Goat Whey Protein-Derived Bioactive Peptides as Pancreatic Lipase and alpha-Amylase Inhibitors

Goat whey protein (GWP) is recognized as a valuable source of bioactive peptides with significant health-promoting properties. In this study, GWP was enzymatically hydrolyzed using a combination of gastrointestinal enzymes-- pepsin, trypsin, and chymotrypsin--to generate peptides. These peptides were identified through high-resolution liquid chromatography-mass spectrometry (HR-LC/MS), resulting in library of 2,883 peptides with lengths ranging from 6 to 44 amino acids. Among them, 40 peptides were predicted to exhibit high bioactivity scores (0.90-1) based on PeptideRanker analysis, with 28 of these being classified as nontoxic. Molecular docking simulations were employed to investigate the interactions of these peptides with pancreatic lipase and -amylase to screening of inhibitors, these two enzymes critical in lipid and carbohydrate metabolism. Several peptides demonstrated strong binding affinities, suggesting their potential as enzyme inhibitors. Notably, peptides WPGIMR and WQDGSWQF showed the highest binding affinity for pancreatic lipase, while AAPFIWL and WQDGSWQF exhibited significant interactions with -amylase. These results shed light on the molecular mechanisms underlying the inhibitory activities of whey protein-derived peptides. They highlight their potential applications as functional food ingredients or natural therapeutic agents for managing metabolic disorders such as obesity and diabetes, advancing the understanding of whey protein hydrolysates in modulating key metabolic enzymes.