Panax ginseng-derived peptides as natural dipeptidyl peptidase-IV inhibitors: screening, binding mechanisms, and potential for glycemic management in functional foods

Panax ginseng is a protein-rich medicinal crop with great potential as a source of bioactive peptides. Dipeptidyl peptidase-IV (DPP-IV) is an important therapeutic target for type 2 diabetes mellitus (T2DM), and natural DPP-IV inhibitory peptides have attracted increasing attention as functional food ingredients. Here, an integrated strategy combining trypsin digestion, machine learning prediction, large language model-assisted screening, Stack DPP-IV analysis, and molecular docking was developed to identify ginseng-derived DPP-IV inhibitory peptides. Three peptides, VLAK, VIDQTK, and IPVAYVK, were selected and experimentally validated, exhibiting IC₅₀ values of 2.66, 3.53, and 2.56 mM, respectively. Molecular docking and molecular dynamics simulations demonstrated that these peptides stably interacted with the DPP-IV active site through hydrogen bonding, electrostatic, and hydrophobic interactions. This study provides a computational-experimental framework for discovering plant-derived DPP-IV inhibitory peptides and highlights the potential of ginseng proteins as valuable resources for functional food development targeting glycemic management.