Molecular insights into the interaction of angiotensin I-converting enzyme (ACE) inhibitors and HEXXH motif

Nutraceuticals and functional foods garner a lot of attention as potential alternative therapies for treatment of (pre)hypertension. Food-derived proteins release large variety of bioactive peptides which are similar in structure to peptide sequences acting in the organism and therefore can modulate their physiological functions. ValPro-Pro (VPP) is a milk-derived tripeptide with assumed mild inhibitory activity against angiotensin-converting enzyme (ACE). Computational (DFT) methods are applied on simplified models of Zn2+-HEXXH binding motif without/with bound inhibitors in order to assess the ability of two pharmaceutical drugs (Captopril and Lisinopril) and Val-Pro-Pro to coordinate with Zn2+-HEXXH binding motif of ACE. Both drugs have significant affinity towards the active site, while the Val-Pro-Pro tripeptide has weaker affinity. The obtained results shed light on the thermodynamic aspects of the inhibitors coordination to the Zn2+-HEXXH binding motif of ACE.

Automated summary

Nutraceuticals and functional foods are gaining attention as potential alternative therapies for (pre)hypertension, with food-derived proteins releasing bioactive peptides that can modulate physiological functions. ValPro-Pro, a milk-derived tripeptide, has mild inhibitory activity against ACE but weaker affinity compared to pharmaceutical drugs. Computational methods were used to assess the coordination of inhibitors with the Zn2+-HEXXH binding motif of ACE, revealing significant affinity of drugs towards the active site.