Discovery of saltiness-enhancing peptides from Hypsizygus marmoreus via virtual screening, multisensory evaluation, electronic tongue, and molecular simulation

This study applied an integrated strategy combining sensory-guided screening, machine learning, and bioinformatics to identify saltiness-enhancing peptides from Hypsizygus marmoreus . Their saltiness-enhancing effect was confirmed by sensory evaluation and electronic tongue analysis. Three peptides (ASHGEGF, GDDWT, and LDDGF) exhibited synergistic or additive effects, increasing both the perceived intensity and the duration of saltiness in NaCl solutions. Molecular docking predicted that these peptides mainly interacted with the TMC4 model through hydrogen bonding, with Lys486, Gln377, Glu235, and Gln482 appearing as recurrent contact residues. Molecular dynamics simulations further supported the stability and close association of the saltiness-enhancing peptide-TMC4 complexes, suggesting their potential to enhance saltiness perception. Density functional theory calculations of frontier orbitals and electrostatic potential provided different patterns of saltiness-enhancing peptides. Collectively, these results propose a screening strategy for saltiness-enhancing peptides from Hypsizygus marmoreus and support their potential as taste enhancers for low-sodium food applications.