The novel angiotensin-I-converting enzyme inhibitory peptides from Scomber japonicus muscle protein hydrolysates: QSAR-based screening, molecular docking, kinetic and stability studies.

[Display omitted] • QSAR model based on 5z-scale was established to predict ACE-I pentapeptides. • Two novel ACE-I peptides were obtained by QSAR model and in silico screening. • PLITT showed the strongest ACE-I activity. • Hydrogen bonding interactions played a critical role in ACE inhibition. • The inhibition mode of PLITT was a mixture of non-competition and competition. Food-derived angiotensin-converting enzyme-inhibitory (ACE-I) peptides have attracted extensive attention. Herein, the ACE-I peptides from Scomber japonicus muscle hydrolysates were screened, and their mechanisms of action and inhibition stability were explored. The quantitative structure–activity relationship (QSAR) model based on 5z-scale metrics was developed to rapidly screen for ACE-I peptides. Two novel potential ACE-I peptides (LTPFT, PLITT) were predicted through this model coupled with in silico screening, of which PLITT had the highest activity (IC 50 : 48.73 ± 7.59 μM). PLITT inhibited ACE activity with a mixture of non-competitive and competitive mechanisms, and this inhibition mainly contributed to the hydrogen bonding based on molecular docking study. PLITT is stable under high temperatures, pH, glucose, and NaCl. The zinc ions (Zn2+) and copper ions (Cu2+) enhanced ACE-I activity. The study suggests that the QSAR model is effective in rapidly screening for ACE-I inhibitors, and PLITT can be supplemented in foods to lower blood pressure. [ABSTRACT FROM AUTHOR]