Molecular elucidation of the identification of novel saltiness‐enhancing peptides and taste mechanism from soybean protein isolate based on transmembrane channel‐like 4 (TMC4)

Abstract BACKGROUND Saltiness‐enhancing peptides serve as excellent natural substitutes for salt, offering advantages such as safety, widespread availability and low taste thresholds. In the present study, we rapidly screened potential saltiness‐enhancing peptides in soybean protein isolate through virtual screening and molecular mechanism analysis. RESULTS This study aimed to identify novel saltiness‐enhancing peptides from soybean protein isolate and further investigated the mechanism underlying their saltiness‐enhancing effects. Four saltiness‐enhancing peptides (DFYNPK, DTFPYPR, SNDVYLPR and LPQDPYQR) were identified through peptidomics, virtual screening and molecular docking. Sensory evaluation and electronic tongue analysis demonstrated that these peptides exhibited significant saltiness‐enhancing effects, with enhancement thresholds of 0.100–0.479 mmol L −1 . Among them, DTFPYPR significantly increased the overall saltiness of a complex system and was capable of replacing approximately 72.9% of the added NaCl. Subsequently, a TMC4 salt receptor model was developed, and molecular docking analysis was performed. The four peptides exhibited strong binding affinity to the TMC4 receptor via hydrogen bonds, hydrophobic interactions and electrostatic interactions, with Glu286, His293, Arg294, Glu323 and Lys685 emerging as critical binding sites. In addition, molecular dynamics simulations demonstrated the reliability of the TMC4 model for the prediction and identification of saltiness‐enhancing peptides. CONCLUSION This study successfully established a rapid screening method for saltiness‐enhancing peptides and identified four saltiness‐enhancing peptides from soybean protein isolate. Furthermore, this study laid a theoretical molecular foundation for the development of salt reduction strategies. It also provides new insights for the swift advancement of plant‐based low‐sodium flavorings. © 2025 Society of Chemical Industry.