Identification of novel saltiness-enhancing peptides from yeast extract and their mechanism of action for transmembrane channel-like 4 (TMC4) protein through experimental and integrated computational modeling.

Excessive consumption of sodium salt is one of the important inducers of cardiovascular and cerebrovascular diseases. The reduction of physical labor and attention to health make research on low-sodium salt imminent. Ultrafiltration, gel filtration, preparative high-performance liquid chromatography, and liquid chromatography with tandem mass spectrometry were employed for further purification and identification of the salty enhancing peptides in yeast extracts. Moreover, human transmembrane channel-like 4 (TMC4) was constructed and evaluated by computer-based methods, and salt-enhancing peptides were identified based on its allosteric sites. PN, NSE, NE and SPE were further determined to be salty enhancing peptides through sensory evaluation, and their taste mechanism was investigated. The results presented here suggest that silicon screening focused on TMC4 allosteric sites and sensory evaluation experiments can greatly increase the discoverability and identifiability of salty enhancer peptides, and this strategy is the first to be applied to the development of salty enhancer peptides.