Traditional fermented sufu is a daily condiment and appetizer, acting as a good source of plant-derived protein and bioactive peptides.To explore the angiotensin converting enzyme (ACE) inhibitory tetrapeptide and investigate the structure-activity relationships, the peptides of oil sufu were isolated using ultrafiltration and solid-phase extraction, and identified using Nano-LC-MS/MS.The potential ACE inhibitory peptides were preliminarily screened by online database, and then the peptides with high ACE inhibitory activity potential were further screened and analyzed using molecular docking, quantum chemical calculation, and quantitative structure activity relationship modeling.Their binding modes, distribution of the frontier molecular orbital, active sites, and inhibitory activities were analyzed.The results showed that peptides with molecular weight <3 kDa had the highest inhibitory activity [IC50=(489.6±26.69) μg/mL], and a total of seven high-potential ACE-inhibitory tetrapeptides were screened after sequences identification.The molecular docking results showed that all seven peptides bound tightly to the receptor through hydrogen bonding, hydrophobic, electrostatic, and metal bonding interactions to exert their inhibitory effects.Quantum chemical results showed that the highest occupied molecular orbitals of the tetrapeptide were mainly distributed on the two-terminal proline (P), and they had a high electronegativity and was easy to become an active site;FALP, GWPT and EGWP had lower energy gap and higher molecular reactivity.The results of quantitative structure activity relationship modeling showed that the parametric characteristics of the amino acid residues at two-terminal of the tetrapeptide had a more significant effect on the IC50 value;the smaller hydrophobicity and stereotropism of the amino acid, and larger electrical properties, the stronger the activity of the peptides.In conclusion, computer-assisted screening of ACE inhibitory peptides in furu was feasible, and the electrical properties of the two-terminal and proline were important to its inhibitory activity, which will provide a reference for the subsequent rapid screening of ACE inhibitory peptides and the study of structure-activity relationship.
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