Shengnan Wang

BACKGROUND: A high‐salt diet poses potential risks to human health, making the search for safe and effective salt‐reduction strategies a research priority. As a novel class of functional components, saltiness‐enhancing peptides have attracted increasing attention due to their natural origin, low taste thresholds, and desirable taste properties. RESULTS: A high‐salt diet poses potential risks to human health. In this study, three novel saltiness‐enhancing peptides (DPR, CTMR and GDEF) were identified from rice bran protein through virtual enzymatic hydrolysis using the PeptideCutter tool of ExPASy. Sensory evaluation and electronic tongue analysis indicated that these peptides exhibited significant saltiness‐enhancing effects, with threshold concentrations ranging from 0.25 to 0.32 mmol L ⁻¹ . DPR, CTMR and GDEF were found to stimulate the secretion of aldosterone in saliva, further confirming their ability to enhance human salt taste sensitivity. CONCLUSION: AlphaFold3 was used to model transmembrane channel‐like protein 4 (TMC4), and molecular docking combined with molecular dynamics simulations was performed to investigate the binding mechanisms between the saltiness‐enhancing peptides and TMC4. It was found that key amino acid residues, such as Arg437, Asp491, Asp530 and Glu531, play important roles in the ligand–receptor interactions, and molecular dynamics simulations further confirmed the binding stability of these interaction sites. This study provides a theoretical basis for the discovery and application of saltiness‐enhancing peptides derived from cereal sources. © 2025 Society of Chemical Industry.