The main goal of this study was to assess the potential proteins of goat milk (i.e. α‐s1‐casein, α‐s2‐casein, β‐casein, κ‐casein, α‐lactoglobulin and β‐lactalbumin) as precursors of antimicrobial peptides (AMPs). Bioinformatics tools such as BIOPEP‐UWM (enzyme action) were used for the in silico gastrointestinal digestion via a cocktail of pepsin, trypsin, and chymotrypsin A. The antimicrobial activity of peptides was predicted by using four algorithms, including Random Forest, Support Vector Machines, Artificial Neural Network and Discriminant Analysis on CAMPR3 online server, which works on Hidden Markov Models. Different online tools predicted the physiochemical properties, allergenicity, and toxicity of peptides as well. In silico gastrointestinal digestion simulation of proteins by enzymes cocktail yielded a total of 83 potential AMPs, with thirteen peptides being confident by all four algorithms. More AMPs were released from β‐casein (21) than from β‐lactoglobulin (16), α‐s1‐casein (15), α‐s2‐casein (12), κ‐casein (11) and α‐lactalbumin (9). A total of 17 peptides were cationic, and the majority of the peptides were extended AMPs. These peptides were released from α‐s1‐casein (SGK, IQK), α‐s2‐casein (SIR, AIH, TQPK), β‐casein (GPVR, AVPQR, AIAR, GVPK, SQPK, PVPQK, IH, VPK), k‐casein (AIPPK, QQR, IAK, TVPAK). All of the AMPs were anticipated to be non‐toxic, and 54 of the 83 peptides were confirmed to be non‐allergic, with the remaining 29 suspected of being allergenic and 31 to be predicted to have good water solubility. Further the molecular docking was used to evaluate the potent dihydropteroate synthase (DHPS) inhibitors. On the basis of ligand binding energy, 17 predicted AMPs were selected and then analyzed by AutoDock tools. Among the 17 AMPs, 3 AMPs were predicted as high‐potent antimicrobial. Based on these findings, in silico investigations reveal that proteins of goat milk are a potential source of AMPs. These peptides can be synthesized and improved for use in the food sector. Practical applications Goat milk is regarded as a high‐quality milk protein source. According to this study, goat milk protein is a possible source of AMPs, and therefore, most important AMPs can be synthesized and developed for use in the food sector.

An in silico approach was used for hydrolysis of sheep milk proteins (α‐s1, α‐s2, β‐casein, κ‐Cn, α‐lactalbumin, and β‐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 (αS1‐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 (β‐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.