Novel sweet peptides YPP, PRP, IVPLFKRDFG, and NPKDGLVPLK identified from Meretrix lyrata bind `TAS1R2`/`TAS1R3`

Sweeteners are crucial in food and beverage industries, but artificial options often face consumer concerns regarding safety and naturalness. There's a growing demand for natural, healthy alternatives. Peptides derived from natural sources offer a promising avenue due to their inherent safety and diverse biological activities. Understanding the molecular interactions between these peptides and human sweet taste receptors (TAS1R2/TAS1R3) is vital for developing effective and targeted natural sweeteners, addressing the gap in identifying specific, potent peptide-based options.

Researchers employed a combined approach of peptidomics to extract and identify peptides from Meretrix lyrata extract. Four novel sweet peptides (YPP, PRP, IVPLFKRDFG, and NPKDGLVPLK) were identified. Molecular docking simulations were then used to predict their binding interactions with the human sweet taste receptor TAS1R2/TAS1R3. Subsequently, these four peptides were chemically synthesized for experimental validation. Their taste profiles were evaluated using an "artificial and intelligent sensory evaluation" system, and their antioxidant and thermal stability were also analyzed.

Molecular docking analysis revealed that hydrogen bonding and hydrophobic interactions are the primary forces driving the binding of these novel peptides to the TAS1R2/TAS1R3 receptor. Key binding sites on the receptor were identified as Ala176, Gln211, Glu217, and Leu173, with Gln, Glu, and Thr residues being critical for the docking process. The "artificial and intelligent sensory evaluation" indicated that the peptide NPKDGLVPLK demonstrated the optimal overall sweetness effect among the four identified peptides. Furthermore, analysis of antioxidant and thermal stability showed that the peptide YPP was a superior performer in these stability assays. These findings underscore the successful integration of computational predictions with experimental validation, providing detailed insights into the molecular mechanisms of sweet taste perception by these novel peptides.