Unveiling antihypertensive and antimicrobial peptides from wine lees: Enzymatic hydrolysis, peptidomics profiling, virtual screening, functional characterization, and molecular docking

Wine lees proteins hydrolysates obtained with alcalase, flavourzyme and protease either individually or in combination displayed varied degrees of angiotensin-converting enzyme inhibitory (ACEi) activity and growth inhibition of food-borne microorganisms. Peptidomics by nano-liquid chromatography-orbitrap tandem mass spectrometry together with virtual screening categorized the peptides according to their bioactivity. High proportion of positive charged peptides in protease hydrolysate associated with a higher growth inhibition activity against Escherichia coli . Prediction of ACEi-active di- and tri-motives encrypted within peptides with scores above 0.90 was performed by in silico simulated gastrointestinal digestion. The peptides released after digestion were predicted as non-toxic, highly soluble, having human intestinal absorption (HIA) and adequate bioavailabilities. Out of these 34 ACEi active sequences liberated, AF, AW, GF, GL, GW, PL, PM and VW showed positive HIA. The prediction of adsorption, digestion, metabolism, excretion and toxicity using physicochemical properties and Lipinski's rule-of-five exposed that the peptides were non-toxic and had desirable drug-like properties (flexibility, lipophilicity, molecular weight, gastrointestinal absorption, and bioavailability). Molecular docking revealed stronger ACEi potential for VW and AW compared to the other structures with binding energies lower than −8.0 kcal mol −1 . Peptides inhibited ACE through hydrogen bonds, Van der Waals interactions and π–π stacking. Insights into the molecular interactions of ACEi peptides with physiological targets are presented, highlighting the potential of wine lees as a source of multifunctional peptides. Prospective multifunctional in vitro and in vivo effects of these sequences, and peptides containing them, need to be evaluated for understanding their potential therapeutic properties.