Dual function antioxidant and anti-inflammatory fish maw peptides: Isolation and structure-activity analysis via tandem molecular docking and quantum chemical calculation

The structure–function relationship of gastrointestinal tract digestion-derived fish maw peptides remains largely unknown. This study aims to elucidate the active sites and cellular bioactivities of these peptides through molecular docking (MD), density functional theory (DFT) computations, in silico bioinformatic analysis, and in cellulo Caco-2 cell studies. In silico screening identified 29 non-toxic, non-allergenic, and water-soluble peptides. Seven peptides exhibited favorable binding to the Keap1-Kelch (2FLU) and TNF-α (2AZ5) proteins. Specifically, peptides WIDPNQG, GFPGER, and FLLFRQ demonstrated the highest electron affinities and smallest HOMO-LUMO energy gaps, suggesting strong free-radical scavenging potential. Both DFT and ex situ MD confirmed the active sites of the seven peptides. The guanidinium group was the dominant active site on six peptides. The isolated peptides improved cellular redox balance, reduced malonaldehyde, and suppressed inflammatory cytokines. This study confirmed DFT computations as a novel tool for elucidating the structure-function relationship of food-derived peptides.