Structural and Antioxidant Comparison Between Native WPI and WPI-Resveratrol Non-Covalent Complex

Population aging has made sarcopenia a growing concern in geriatric health. Protein–polyphenol non-covalent complexes can serve as carrier systems that improve the stability and bioactivity of natural antioxidants. This study refined the preparation parameters for the non-covalent complex of whey protein isolate (WPI) and resveratrol (RES), achieving protein digestibility of 83.60 ± 0.50% and DPPH scavenging of 52.41 ± 0.58% at pH 7.0, a WPI:RES molar ratio of 1:1, and a reaction time of 1.5 h. Relative to free WPI, the complex improved DPPH scavenging by 21.66% while preserving protein digestibility. The binding mode, interaction forces, and conformational evolution were investigated via spectroscopic experiments, docking studies and molecular dynamics simulations. RES selectively bound to the surface of β-lactoglobulin in WPI through hydrophobic interactions and hydrogen bonding, with a docking score of −6.366 kcal/mol and an MM-GBSA binding free energy of −30.48 kcal/mol. The complex maintained a highly stable conformation throughout the 100 ns molecular dynamics simulation. In conclusion, this study elucidated the structural changes of WPI upon non-covalent resveratrol binding. The WPI-RES complex exhibited enhanced DPPH radical scavenging activity while preserving protein digestibility, with potential implications for functional food development in sarcopenia management.