Prediction and evaluation of purine-binding peptides using integrated molecular descriptors and docking analysis

Peptides and purines frequently coexist in food systems and can form specific molecular interactions, which may influence the physicochemical properties and bioavailability of purines. However, the structural basis and binding mechanisms of these peptide-purine interactions remain poorly understood. This study established a comprehensive screening approach combining molecular docking and descriptor analysis to evaluate peptide-purine binding interaction. The analysis revealed that strong-binding peptides were likely characterized by reduced cyclic structures and aromatic rings, with elevated electron-donor groups primarily composed of N and O atoms (p < 0.0001). These electron-rich functional groups appeared to enhance the formation of hydrogen bonds, which could play a crucial role in stabilizing peptide-purine complexes. Among various dietary purines, hypoxanthine emerged as the predominant species in processed meat products, warranting particular attention. Fluorescence spectroscopy experiments validated the computational predictions, confirming that the tetrapeptide WDQW (Peptide Purine Binding Score: -3.32) formed stable complexes with hypoxanthine exhibiting static quenching characteristics, primarily driven by hydrophobic interactions and hydrogen bonding. This investigation provides fundamental insights into peptide-purine binding mechanisms and establishes a screening platform for identifying peptide sequences with enhanced purine-binding properties, which might be valuable for modulating purine bioavailability in food systems.