ACE Inhibitory Peptide Tailored Preparation, Screening, and Interaction Mechanism via Computer-Assisted Experimental Studies

Conventional ACE-inhibitory peptide production methods suffer from low yield, suboptimal activity, and extensive optimization. This study introduces DeepAngio, a novel model to address these limitations and enable targeted release. DeepAngio demonstrates high performance in screening (98.80% accuracy, 99.63% precision, and 96.44% specificity) and classification (88.24% accuracy, 86.76% precision, and 95.16% specificity) validated through 10-fold cross-validation. Moreover, DeepAngio facilitated the development of a method for directional preparation of tuna meat hydrolysates with notable ACE inhibitory activity (IC 50, 31.27 ± 0.72 μg/mL). Three novel potent ACE inhibitory peptides were screened from the hydrolysate: LLRP (IC 50, 3.44 ± 0.19 μM), LHWPR (IC 50, 17.67 ± 1.53 μM), and RFLR (IC 50, 42.52 ± 7.50 μM). The peptides inhibited ACE activity via mixed-competitive (LLRP and RFLR) or competitive (LHWPR) mechanisms, forming stable complexes. Spectroscopic and molecular docking analyses revealed distinct binding modes for each peptide.