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

Abstract

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.

Cocoa (Theobroma cacao L.) Seed Proteins’ Anti-Obesity Potential through Lipase Inhibition Using In Silico, In Vitro and In Vivo Models

“…In other studies carried out with fish tripeptides from Larimichthys crocea or Oncorhynchus mykiss , good absorption BBB and HIA values were also obtained [ 30 ]. Another in silico assay with ADMET was performed with soybean tripeptides, highlighting that seven peptides had a good probability of absorption in HIA and four in BBB [ 31 ]. Based on the favorable ADMET characteristics, this tool is recommended for future research with peptides and other molecules in the production of functional foods.…”

Characteristics of Biopeptides Released In Silico from Collagens Using Quantitative Parameters

“…ADMET calculation would significantly aid the in silico evaluation of the potential bioactivity of peptides. To date, there were only few publications including the calculation of ADMET properties of bioactive peptides from food [85][86][87][88].…”

Structure–activity relationship and molecular docking analysis of cysteine‐containing dipeptides as antioxidant and ACE inhibitory

“…All cysteine‐containing dipeptides had low absorption to the central nervous system; consequently, they less affected the normal function of the brain. Considering about metabolism, except CN and CQ, most of the cysteine‐containing dipeptides displayed neither substrates nor inhibitors for CYP, indicating these peptides would not lead to drug–drug interactions during the different stages of the metabolism cycle (Zhao et al ., 2019). Moreover, according to the behaviours of ERB, ARB and TRB, these peptides were not endocrine disrupters, so they did not affect the normal functions associated with hormones.…”

“…Considering the toxicity and bioavailability, the metabolic information about cysteine‐containing dipeptide was so important that it was necessary to conduct an in silico ADME prediction. The ADME prediction was processed by an online tool admetSAR (http://lmmd.ecust.edu.cn/admetsar2/) (Zhao et al ., 2019). To predict the adsorption and distribution of these peptides, human intestinal absorption (HIA), blood–brain barrier (BBB) and human oral bioavailability (HOB) were chosen to predict the adsorption and distribution properties of these peptides; cytochrome P450 (CYP) inhibitory promiscuity (CYPIP), CYP2C9 substrate, CYP2D6 substrate, oestrogen receptor binding (ERB), androgen receptor binding (ARB) and thyroid receptor binding (TRB) were selected to reflect their metabolic behaviours; and ames mutagenesis (AM), carcinogenicity (binary) and human either‐a‐go‐go inhibition (HEI) were selected to evaluate their toxicity.…”