Identification novel salty-enhancing peptides from sea cucumber collagen: AlphaFold2 modeling and molecular simulation

Abstract

Abstract This study aimed to extract novel salty-enhancing peptides from the collagen of sea cucumber. The model of the transmembrane channel-like 4 (TMC4) salt taste receptor was constructed by AlphaFold2 de novo model, and the interaction between peptides and salt taste receptor was studied by molecular dynamics (MD) simulation. The results revealed that 99.4% of amino acid residues in the Ramachandran Plot of the TMC4 model resided within the allowed region, thereby substantiating the rationality of the model. The molecular docking results indicated that Gln 279, Glu 92, and Lys 278 may be the key amino acids binding to the TMC4 receptor. The CSRH and KDINNRF showed significant enhancement in saltiness compared to the control group (2.62 ± 0.04), with saltiness values of 3.01 ± 0.00 and 2.86 ± 0.04, respectively. In addition, MD simulation results showed that TMC4 saltiness receptors formed stable RMSD and Rg with salty-enhancing peptides at 0–25 ns simulation time. This study verified that CSRH and KDINNRF are effective salty-enhancing peptides, and also provided a theoretical basis for the discovery of new salty-enhancing peptide resources in marine organisms.