Novel antioxidant peptides identified from coix seed by molecular docking, quantum chemical calculations and invitro study in HepG2 cells

This aim of the study was to identify potent antioxidant peptides sourced from coix seed, analyze the structure–activity relationship through molecular docking and quantum chemical calculation. Molecular docking results showed that among thirteen peptides selected in silico, eight had favourable binding interaction with the Keap1-Kelch domain (2FLU). Promising peptides with significant binding scores were further evaluated using quantum calculation. It was shown that peptide FFDR exhibited exceptional stability, with a high energy gap of 5.24 eV and low Highest Occupied Molecular Orbitals (HOMO) and Lowest Unoccupied Molecular Orbitals (LUMO) values. Furthermore, FFDR displayed the capacity to enhance the expression of Nrf2-Keap1 antioxidant genes (CAT, SOD, GSH-Px) and improved cellular redox balance by increasing reduced glutathione (GSH) while reducing oxidized glutathione (GSSG) and malonaldehyde (MDA) levels. These findings highlight the potential of coix seed peptides in developing novel, effective and stable antioxidant-based functional foods.