College of Food Science and Engineering, Bohai University, Jinzhou, P.R. China.
Lab of Nutrition and Functional Food, Jilin University, Changchun, P.R. China.
J Food Biochem. 2019 Sep;43(9):e12975. doi: 10.1111/jfbc.12975. Epub 2019 Jul 5.
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 IC 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.
大豆衍生肽的广泛应用目前受到肽鉴定挑战的限制。在本工作中，应用计算机和体外分析从大豆蛋白中鉴定 ACE 抑制三肽。大豆蛋白通过 PeptideCutter 切割。然后，选择未知三肽进行溶解度估计和 ADME 预测。随后，Discovery Studio 用于评估 ACE 和三肽之间的相互作用机制。最后，通过反相高效液相色谱法 (RP-HPLC) 方法验证理论 ACE 抑制三肽的体外活性。结果表明，DMG 是一种有效的 ACE 抑制肽。细胞实验表明，DMG 对 HEK-293 细胞没有细胞毒性作用。分子对接结果表明，DMG 与 ACE 的活性位点 (Gln281、His353、Ala354、Glu384、Lys511、His513 和 Tyr520) 结合良好。此外，DMG 对 ACE 具有很强的抑制活性，IC 值为 3.95±0.11 mM。实际应用：本研究表明大豆是获得 ACE 抑制肽的潜在蛋白质资源。同时，虚拟筛选方法是替代新兴营养领域经典方法的可行途径。此外，本研究为开发无副作用的 ACE 抑制肽食品提供了理论依据。
