Novel ACE inhibitors derived from soybean proteins using in silico and in vitro studies

The widespread application of soybean-derived peptides is currently limited due to the challenges in the identification of peptides. In the present work, in silico and in vitro analysis were applied to identify ACE inhibitory tri-peptides from soybean protein. The soybean protein was cleaved by PeptideCutter. Then, unknown tri-peptides were selected to solubility estimation and ADME prediction. Subsequently, Discovery Studio was applied to evaluate the interaction mechanism between ACE and tri-peptides. Finally, in vitro activity of theoretical ACE inhibitory tri-peptides was verified by RP-HPLC method. As a result, DMG was selected as a potent ACE inhibitory peptide. Cell experiment showed that DMG had no cytotoxic effects on HEK-293 cells. And molecular docking results indicated that DMG contacted well with ACE's active sites (Gln281, His353, Ala354, Glu384, Lys511, His513, and Tyr520). Furthermore, DMG could exert potent activity against ACE, with IC50 value of 3.95 ± 0.11 mM. Practical applications Present research showed soybean is a potential protein resource to obtain ACE inhibitory peptides. Simultaneously, virtual screening method is a feasible way to substitute for classical method in emerging nutritional fields. What's more, present study provides a theoretical basis for industrial research on foodstuff for ACE inhibitory peptides without side effects.