Discovery of sunflower-derived umami peptides via machine learning and molecular dynamics simulation of their interactions with the T1R1/T1R3 receptor.

Introduction: Umami recognition relies on T1R1/T1R3 binding with umami peptides, but the interaction mechanisms remain unclear. This study aims to reveal the taste mechanisms of four potential umami peptides at both sensory and molecular levels. Methods: Electronic tongue evaluations were performed to assess umami and richness intensities. Principal component analysis (PCA) was used to discriminate the peptides. Molecular docking and 200 ns molecular dynamics (MD) simulations were conducted to characterize the binding modes and conformational dynamics of peptide-receptor complexes. Results: Electronic tongue evaluation showed that ELLADMK exhibited the highest umami (1.05) and richness (1.77) intensities, followed by LEELMDK (umami: 0.97), HELDTK (umami: 0.72), and ADVLEK (umami: 0.49). PCA effectively discriminated these peptides, accounting for 93.8% of the total variance (PC1: 71.8%, PC2: 22.0%). Molecular docking and 200 ns MD simulations revealed that umami peptide binding decreased the conformational stability of the Venus flytrap domain, induced conformational expansion (e.g., in the ELLADMK system, RMSD increased from 2-4 Å to 8-10 Å, and Rg increased from 31.0-31.5 Å to 32.0-32.5 Å), and altered solvent accessibility in key regions. Notably, ELLADMK exhibited the most prominent modulatory effect. Discussion: These findings clarify the sensory and molecular mechanisms underlying umami peptide recognition. The pronounced modulatory effect of ELLADMK suggests its potential as a highly active umami peptide. Overall, this study provides a theoretical basis for the targeted screening of highly active umami peptides and for precise flavor regulation.