Valorization of yak bone collagen byproducts: computational screening and experimental validation of anti-aging peptides targeting MMP-1Download PDF Download PDF ArticleOpen accessPublished: 22 October 2026Yuyang Liu1,Yan Zhang1,Qida Li1,Jinsheng Zhuang1,Wannan Li1 &…Weiwei Han ORCID: orcid.org/0000-0002-1931-93161 npj Science of Food (2026) Cite this articleView saved research We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.AbstractValorization 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 IC50 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.AcknowledgementsThis work was supported by the Graduate Innovation Fund of Jilin University (Grant No. 2026CX134). The funder had no role in the study design, data collection and analysis, interpretation of the results, preparation of the manuscript, or decision to submit the manuscript for publication.FundingThe authors received no specific funding for this work.Author informationAuthors and AffiliationsKey Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Edmond Fischer Cell Signaling Laboratory, School of Life Sciences, Jilin University, Changchun, ChinaYuyang Liu, Yan Zhang, Qida Li, Jinsheng Zhuang, Wannan Li & Weiwei HanAuthorsYuyang LiuView author publicationsSearch author on:PubMed Google ScholarYan ZhangView author publicationsSearch author on:PubMed Google ScholarQida LiView author publicationsSearch author on:PubMed Google ScholarJinsheng ZhuangView author publicationsSearch author on:PubMed Google ScholarWannan LiView author publicationsSearch author on:PubMed Google ScholarWeiwei HanView author publicationsSearch author on:PubMed Google ScholarCorresponding authorsCorrespondence to Wannan Li or Weiwei Han.Ethics declarationsCompeting interestsThe authors declare no competing interests.Additional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.Supplementary informationRights and permissionsOpen Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Reprints and permissionsAbout this article