Identification of novel ACE inhibitory peptides from Nannochloropsis oculata through peptidomics, in silico screening and molecular docking.

The protein of Nannochloropsis oculata, a single-cell marine microalga, was hydrolyzed by different enzymes. The low-molecular-weight fraction of the trypsin hydrolysate exhibited the best angiotensin-converting enzyme inhibitory (ACEI) activity and possessed diverse peptide sequences. After in silico screening and in vitro verification, three novel high-activity peptides were identified. Among them, GPGPFTVF exhibits the lowest IC50 value (39.77 ± 1.42 μM), followed by PGPAIF (52.03 ± 2.19 μM) and WDPLGF (107.96 ± 4.84 μM). Molecular docking shows that these peptides are bound to ACE via the residues around S1 and S2 pockets and the Zn2+ domain. Hydrogen bond is the most important force for the molecular interaction, and all three peptides inhibit ACE activity via competitive inhibition mode. Further simulated gastrointestinal digestion illustrates that the ACE-I activity is stable with little fluctuation. This study reveals that N. oculata is a promising source for ACE-I peptide not only because of its sequence diversity but also its high activity.