Umami peptides are known for enhancing the taste experience by binding to oral umami T1R1 and T1R3 receptors. Among them, small peptides (composed of 2-4 amino acids) constitute nearly 40% of reported umami peptides. Given the diversity in amino acids and peptide sequences, umami small peptides possess tremendous untapped potential. By investigating 168,400 small peptides, we screened candidates binding to T1R1/T1R3 through molecular docking and molecular dynamics simulations, explored bonding types, amino acid characteristics, preferred binding sites, etc. Utilizing three-dimensional molecular descriptors, bonding information, and a back-propagation neural network, we developed a predictive model with 90.3% accuracy, identifying 24,539 potential umami peptides. Clustering revealed three classes with distinct logP (-2.66 ± 1.02, -3.52 ± 0.93, -2.44 ± 1.23) and asphericity (0.28 ± 0.12, 0.26 ± 0.11, 0.25 ± 0.11), indicating significant differences in shape and hydrophobicity (P < 0.05) among potential umami peptides binding to T1R1/T1R3. Following clustering, nine representative peptides (CQ, DP, NN, CSQ, DMC, TGS, DATE, HANR, and STAN) were synthesized and confirmed to possess umami taste through sensory evaluations and electronic tongue analyses. In summary, this study provides insights into exploring small peptide interactions with umami receptors, advancing umami peptide prediction models.
Keywords: Back propagation neural network; Molecular descriptor; Molecular docking; Umami peptide.