Exploring the potential of calcium-chelating peptides from aquatic sources: Structure-activity relationship, computational simulation, and stability mechanism analysis.

Aquatic products are rich in high-quality proteins, and aquatic proteins derived calcium-chelating peptides (CCPs) are regarded as promising calcium fortifiers for enhancing calcium absorption. However, a systematic understanding of their structure-activity relationships, interaction mechanisms elucidated through computational simulations, and stability in the gastrointestinal environment is still lacking. Therefore, this review summarizes recent advancements in aquatic-derived CCPs, spanning from preparation and characterization to in-depth analysis of their structure-activity relationships and stability mechanisms. Computational techniques have significantly advanced mechanistic insights into peptide-calcium interactions. Molecular docking and molecular dynamics simulations can predict the initial binding conformations and dynamic stability of peptide‑calcium chelates, while quantum chemical calculations can accurately determine key chelating sites and elucidate the underlying coordination mechanisms. Nonetheless, developing novel force fields and improving simulation accuracy are essential for in-depth elucidation of the chelation mechanism. The abundance and positions of acidic and hydrophobic amino acids in peptides influence calcium-chelating ability. Coordinate bonds are the primary force in calcium chelation, which rely on lone pairs of electrons donated by oxygen atoms in phosphate, carboxyl, and carbonyl groups. Additionally, although CCPs exhibit excellent stability, component competition (e.g., phytic acid) and enzymatic degradation in the gastrointestinal tract may disrupt the calcium-peptide chelation. Chemical modification, liposomal encapsulation, and microencapsulation hold potential for protecting peptide‑calcium chelates. This review aims to provide a theoretical foundation for advancing mechanistic insights into CCPs, their application as high-efficiency calcium supplements in functional foods, and future development of industrialized CCPs-based nutraceuticals.