Valorization of yak bone collagen byproducts: computational screening and experimental validation of anti-aging peptides targeting MMP-1

Abstract Valorization of yak collagen byproducts offers a sustainable route to food-derived bioactive peptides. To prioritize candidate peptides from yak collagen-derived sequences, we developed AgeAttnMLP, an ESM-2-based screening model that achieved an AUC of 0.891 under conventional five-fold cross-validation and 0.879 under an additional cluster-aware grouped evaluation. Screening of yak collagen sequences followed by Alcalase-guided in silico hydrolysis identified TGPPGPSGI, GEPGAPGE, and GPSGEPGTA as lead candidates. GEPGAPGE showed the strongest MMP-1 inhibition, with an IC 50 of 126 μg/mL. Molecular dynamics simulations and MM-PBSA analysis suggested that peptide binding destabilized the β-sheet spanning residues 76–78 near the catalytic region, potentially affecting substrate recognition. Under the tested conditions, all three peptides extended the lifespan of Caenorhabditis elegans, with the greatest effect observed for GPSGEPGTA at 7.5 mg/mL. These findings establish an integrated computational–experimental strategy for discovering collagen-derived peptides and support the value-added utilization of yak collagen byproducts as potential functional food ingredients.