Identification, inhibition modes, and molecular docking of ACE inhibitory peptides derived from Cheddar cheese

Herein, changes in the angiotensin-converting enzyme (ACE) inhibitory activity in Cheddar cheese during ripening (0–8 months) were studied, and the specific inhibitory types and modes of ACE inhibitory peptides were analyzed. The ACE inhibitory activity of Cheddar cheese was highest after 6 months (68.4%), and the ACE inhibitors of water-soluble extracts at this stage were mainly concentrated below 3 kDa. Six peptides with ACE inhibitory activity were isolated and purified from these peptides, and the inhibition modes of these peptides were studied. The results showed that VRYL and YLGY were competitive inhibitory peptides, RYL was a non-competitive inhibitory peptide, and TTMP was a mixed inhibitory peptide. Through the simulation of molecular docking sites, it was found that VRYL formed nine hydrogen bonds in the docking model and exhibited the highest ACE inhibitory activity. This study provides key insights for the development of functional cheeses and the extraction of ACE inhibitory peptides from Cheddar cheese.