Virtual screening of salty peptides from enzymatic and fermented products of wheat gluten and its molecular mechanism of interaction with TMC4 receptor.

The health risks associated with excessive sodium intake have prompted an exploration of natural salt substitutes. This study was oriented to explore the salty peptides from enzymatic and fermented products of wheat gluten (WG) with different degrees of hydrolysis (DH) using ultrafiltration, mass spectrometry identification, and machine learning. The results showed a substantial positive correlation between the perception of saltiness and the presence of tripeptides and tetrapeptides. Combined molecular docking and molecular dynamics simulations, eight potential salty peptides (YRAF, NFRP, RAFL, YDFL, GDW, FRPA, WDPL, WYD) were identified based on interactions with the TMC4 receptor. The hydrogen bonds dominated the docking process. Point mutations validated the key role of residues ARG294, GLU323, and VAL322 in saltiness perception. Integration of electronic tongue with sensory validation revealed that WYD exhibited the most outstanding saltiness effect. This study provides a theoretical foundation for the application of WG in the field of salt reduction.