Screening of salty peptides from enzymatic hydrolysates of Meretrix lyrata based on interaction with the TMC4 receptor.

To elucidate the salty mechanism of salty peptides, 152 salty peptides were rapidly screened from enzymatic hydrolysates of Meretrix lyrata based on interaction with the TMC4 receptor. The results revealed that these salty peptides are enriched in residues of Leu, Asp and Glu, with their N- and C-terminals primarily composed of hydrophobic and polar amino acid residues, which caused the acidic amino acid residues and their related sequences to become vital "salty sequences" within the peptides. Furthermore, salty peptides could notably alter TMC4 receptor's surface morphology, characterized by enhanced surface roughness. Salty peptides could primarily interact with TMC4 receptor via hydrogen and hydrophobic bonds, averaging binding energy of -7.3 kcal/mol. The residues Arg506, Leu520, Gln524, Glu525 and Gln527 were the key binding sites for hydrogen bonds, while Ile426 and Leu520 residues were the key binding sites for hydrophobic bonds. Similar to NaCl, four salty peptides demonstrated strong-affinity interaction with the TMC4 receptor, with affinity (Kd) ranging from 1.766 × 10 to 3.427 × 10 M. Moreover, three salty peptides (TWDLL, EDFLLA and VDEVLRL) exhibited exceptional saltiness, equivalent in strength to the same NaCl concentration. These findings provide new perspectives for studying the interaction between salty peptides and salty receptors.