Mining Bovine Milk Proteins for DPP-4 Inhibitory Peptides Using Machine Learning and Virtual Proteolysis  

作　　者：Yiyun Zhang Yiqing Zhu Xin Bao Zijian Dai Qun Shen Liyang Wang Yong Xue 

机构地区：[1]National Engineering and Technology Research Center for Fruits and Vegetables,College of Food Science and Nutritional Engineering,China Agricultural University,Beijing 100083,P.R.China [2]National Center of Technology Innovation (Deep Processing of Highland Barley) in Food Industry,China Agricultural University,Haidian District,Beijing 100083,P.R.China [3]School of Clinical Medicine,Tsinghua University,Beijing 100084,P.R.China

出　　处：《Research》2025年第1期410-420,共11页研究(英文)

基　　金：supported by the National Key Research and Development Project(2018YFE0206300-02).

摘　　要：Dipeptidyl peptidase-IV(DPP-4)enzyme inhibitors are a promising category of diabetes medications.Bioactive peptides,particularly those derived from bovine milk proteins,play crucial roles in inhibiting the DPP-4 enzyme.This study describes a comprehensive strategy for DPP-4 inhibitory peptide discovery and validation that combines machine learning and virtual proteolysis techniques.Five machine learning models,including GBDT,XGBoost,LightGBM,CatBoost,and RF,were trained.Notably,LightGBM demonstrated superior performance with an AUC value of 0.92±0.01.Subsequently,LightGBM was employed to forecast the DPP-4 inhibitory potential of peptides generated through virtual proteolysis of milk proteins.Through a series of in silico screening process and in vitro experiments,GPVRGPF and HPHPHL were found to exhibit good DPP-4 inhibitory activity.Molecular docking and molecular dynamics simulations further confirmed the inhibitory mechanisms of these peptides.Through retracing the virtual proteolysis steps,it was found that GPVRGPF can be obtained fromβ-casein through enzymatic hydrolysis by chymotrypsin,while HPHPHL can be obtained fromκ-casein through enzymatic hydrolysis by stem bromelain or papain.In summary,the integration of machine learning and virtual proteolysis techniques can aid in the preliminary determination of key hydrolysis parameters and facilitate the efficient screening of bioactive peptides.

关 键 词：DPP inhibitors virtual proteolysis techniquesfive machine learning virtual proteolysis bovine milk proteins bovine milk proteinsplay bioactive peptides 

分 类 号：TS252.1[轻工技术与工程—农产品加工及贮藏工程]