Novel angiotensin-converting enzyme (ACE) inhibitory mechanism of peptides from Macadamia integrifolia antimicrobial protein 2 (MiAMP2).

This work aimed to identify novel angiotensin-converting-enzyme (ACE) inhibitory peptides from Macadamia integrifolia antimicrobial protein 2 (MiAMP2). The MiAMP2 protein was hydrolyzed through in silico digestion, and the generated peptides were screened for ACE inhibitory activity. The in silico enzyme digestion results revealed that 18 unreported peptides were obtained using AHTPDB and BIOPEP-UWM, and none were thought to be toxic based on absorption, distribution, metabolism, and excretion (ADMET) prediction. PGPR, RPLY, MNPQR, and AAPR were predicted to exhibit good biological activity. The molecular docking results revealed that the four peptides tightly bound to the active pocket of ACE via hydrogen bonds and hydrophobic interactions, among which RPLY and MNPQR bound to ACE more strongly. The in vitro assay results confirmed that RPLY and MNPQR peptides inhibited ACE via competitive manner. These results provide theoretical guidance for the development of novel foodborne antihypertensive peptides from Macadamia nut proteins. PRACTICAL APPLICATIONS: This study provides new insight on the inhibitory potential of Macadamia nut peptides against ACE, which may be further applied to the development of antihypertensive peptides in the medical industry.