In silico identification of antidiabetic and hypotensive potential bioactive peptides from the sheep milk proteins-a molecular docking study

An in silico approach was used for hydrolysis of sheep milk proteins (alpha-s1, alpha-s2, beta-casein, kappa-Cn, alpha-lactalbumin, and beta-lactoglobulin) by gastrointestinal enzymes in order to generate bioactive peptides (BAPs) that can inhibit ACE and DPP-IV. Sheep milk proteins showed higher similarity with goat milk proteins. These data were acquired via the Clustal Omega tool to perform sequence alignment analysis. The BIOPEP-UWM database was used to examine the ability of sheep milk protein sequences to generate BAPs, which included a description of their potential bioactivity as well as the frequency of fragments with specified activities. Using the Enzyme(s) action tool (BIOPEP-UWM), digestive enzymes pepsin, trypsin, and chymotrypsin, and three enzyme combinations were selected to computationally hydrolyze milk proteins for obtaining information about ACE and DPP-IV inhibitory peptides. Other online programs were used to test potential peptides for bioactivity, toxicity, and physicochemical properties. BAPs produced from PTC-hydrolyzed proteins were analyzed using a peptide ranker, and their inhibitory effects on ACE and DPP-IV were determined using molecular docking. Consequently, the results of molecular docking analysis show that the peptide PSGAW (alpha S1-Cn f155-159) binds to DPP-IV with binding energy (-8.9 kcal/mol). But in the case of ACE, two potential BAPs were selected: QPPQPL (beta-Cn f161-166) and PSGAW. These two BAPs revealed a higher binding affinity for ACE with a binding energy of -9.8 kcal/mol. Thus, the results showed that sheep milk proteins were a promising source of antidiabetic and hypotensive peptides. However, experimental and pre-clinical studies are necessary to assay their therapeutic effects. Practical applications Sheep milk proteins are known as a high-quality milk protein resource. Effective enzymatic hydrolysis of sheep milk proteins can release bioactive peptides and also release potential ACE and DPP-IV inhibitory peptides. This in silico study specifies a theoretical root for sheep milk proteins as a novel source of potential bioactive peptides and may offer guidance for invitro hydrolysis of proteins for the production of bioactive peptides valuable for human consumption.

Automated summary

An in silico study was conducted to investigate the hydrolysis of sheep milk proteins and the generation of bioactive peptides with ACE and DPP-IV inhibitory activity. The results showed that sheep milk proteins have the potential to be a source of antidiabetic and hypotensive peptides.