Identification and molecular mechanisms of novel α-glucosidase inhibitory peptides from Xundian cured beef: In vitro, molecular docking, and molecular dynamics studies

Xundian cured beef (XD-NGB) is renowned for its distinctive flavor and nutritional value, but the functional potential of its protein-derived peptides remains largely unknown. This study aimed to identify α-glucosidase inhibitory peptides in XD-NGB by integrating peptidomics, in silico analysis, and in vitro experiments, and to explore the mechanisms underlying their activity. A total of 1151 peptides were identified using LC-MS/MS. Two non-toxic, water-soluble peptides with favorable metabolic properties and α-glucosidase inhibitory activity (VGSYEDPYH, IC 50 = 1.55 mM; APILVDGKD, IC 50 = 2.02 mM) were screened based on amino acid composition, physicochemical properties, and in silico analysis. Circular dichroism (CD) spectroscopy revealed that both peptides induced a loose and disordered α-glucosidase conformation by decreasing α-helix content while increasing β-sheet and random coil content in its secondary structure. Molecular docking and molecular dynamics simulations demonstrated that VGSYEDPYH and APILVDGKD formed stable complexes with the active site residues of α-glucosidase through hydrogen bonding, hydrophobic interactions, van der Waals forces, and electrostatic interactions, thereby inhibiting α-glucosidase activity. These findings suggest that peptides derived from XD-NGB show great promise as functional food components, offering fresh insights into their potential nutritional value and future applications.