A novel Angiotensin-I-converting enzyme (ACE) inhibitory peptide IAF (Ile-Ala-Phe) from pumpkin seed proteins: in silico screening, inhibitory activity, and molecular mechanisms.

Pumpkin seed proteins with desirable nutritional properties have attracted great interest as an innovative source of bioactive peptides with beneficial effects in recent years. The current study aimed to screen novel ACE inhibitory peptides from pumpkin seed proteins by in silico approach and further elucidate the underlying inhibition mechanisms. A novel tripeptide, IAF (Ile-Ala-Phe) with acceptable bioavailability properties exhibited considerable ACE inhibitory ability with an IC50 of 19.87 ± 0.50 μM. Molecular docking study showed that IAF could bound with key residues in the active site of ACE. Further molecular dynamics (MD) simulation suggested that the simulation systems reached equilibrium after 5 ns and that ACE and IAF can form complex in stabilization. Moreover, MD analysis revealed that the hydrogen bonds interactions between IAF and two key residues (His513 and Glu162) of ACE and the chelation between O3 atom of IAF and Zn2+ play more important roles in the stabilization for ACE–IAF complex, which might contribute significantly to the ACE inhibitory activity. Our study indicated that the novel and potential ACE inhibitory peptide IAF from pumpkin seed proteins can be considered as a promising candidate for controlling hypertension. [ABSTRACT FROM AUTHOR]