Pei-Gee Yap, Chee-Yuen Gan, Premy Puspitawati Rahayu, Nurul Huda
Human, horse, cow, buffalo, goat, and camel milk are essential protein sources with diverse health-promoting properties. Understanding their digestibility, bioactive potential, and safety is increasingly relevant for the formulation of functional foods, infant formulas, and specialized nutrition products. In this review, bioinformatics, artificial intelligence (AI), and peptidomics were integrated to assess the nutritional and bioactive potentials of milk proteins and their peptides. Using in silico enzymatic digestion and peptide databases, the milk protein digestibility, amino acid content, peptide bioactivities, toxicity, and allergenicity were systematically assessed. This is followed by comparative validation with published literature. Analysis of protein degree of hydrolysis revealed α-lactalbumin with superior digestibility across all species, compared to κ-casein and β-lactoglobulin. Amino acid profiling indicated that cow and buffalo milk proteins are overall richer in essential amino acids. Peptides released after simulated pepsin, trypsin, and chymotrypsin digestion showed angiotensin-converting enzyme (ACE), dipeptidyl peptidase-IV (DPP-IV), and antioxidant activities across species. ToxinPred screening identified three toxic peptides, while AllerCatPro screening identified 49 allergenic peptides from cow, buffalo, and goat milk proteins. Overall, these findings allowed the recommendation of species-specific milks tailored for infant nutrition, elderly care, athletic performance, and hypoallergenic applications, and simultaneously allowed early detection of harmful peptides. The combined use of bioinformatics, AI, and peptidomics presents a powerful framework for guiding future research and formulation of milk and milk-derived peptides in functional foods and personalized nutrition. © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Analytical Biochemistry Research Centre (ABrC), Universiti Sains Malaysia, Penang, Malaysia; Faculty of Animal Science, Universitas Brawijaya, East Java, Malang, Indonesia; Postgraduate School, Universitas Brawijaya, East Java, Malang, Indonesia
