Unraveling amino acid sequence features that confer high calcium-binding capacity to soybean peptides and improve absorption in caco-2 cells

Structure–activity relationship of food-derived peptides is a hotspot for nutrient interactions. Some studies have also improved the ability of these chelates to promote calcium absorption. However, whether the structures enabling calcium binding also influence absorption has not been studied in detail. Our previous research found that structural features, such as aspartic acid near the center of the N-terminal or consecutive aspartic acids, enhancing peptide calcium-binding capacity. Although the GGDLVS peptide exhibits these features, its effect on calcium absorption remains unclear. This study investigated chelates derived from peptides with or without these structures. The results indicated that chelates with this structure more effectively promoted Caco-2 cell calcium absorption and upregulated calcium channel protein TRPV6 expression. Molecular docking showed that the structure promoted protein interaction, facilitating calcium accumulation at the channel entry. Molecular dynamics simulations showed that the chelate structure promoted protein activation, stabilized conformation, and increased subsequent hydrogen bond formation.