The purpose of this study was to screen the xanthine oxidase (XO) inhibitory peptides from egg white proteins through virtual hydrolysis, in vitro activity validation, and molecular docking. The results demonstrated that tripeptide EEK from ovalbumin exhibited potent XO inhibitory activity with an IC₅₀ value of 141 µmol/L. The molecular docking results showed that tripeptide EEK bound with the active center of XO via 3 carbon hydrogen bond interactions, 2 salt bridges, 5 conventional hydrogen bond interactions, and 4 attractive charge interactions. The residues Glu802, Phe1009, and Arg880 may play key roles in the XO catalytic reaction. Especially, the key intermolecular forces of inhibiting XO activity may be special type of hydrogen bonds including carbon hydrogen bond interactions and attraction charge interactions. The novel tripeptide EEK is potential candidates for controlling hyperuricemia.

Inhibition of beta-site APP cleaving enzyme1 (BACE1) is one of the most promising therapeutic approaches for Alzheimer's disease. To find natural products for the treatment of Alzheimer's disease, absorption, distribution, metabolism, excretion and toxicity (ADMET) properties and in vitro BACE1 inhibitory activity of the peptides isolated from egg albumin were evaluated. Then, molecular docking and molecular dynamics simulation were used to explain the molecular mechanism of the interactions between BACE1 and peptides. The IC₅₀ value of peptide KLPGF, with satisfactory ADMET properties, against BACE1 was (8.30 ± 0.56) mmol/L. Molecular docking revealed that KLPGF contacted with the residues of BACE1's active sites through twelve hydrogen bonds interactions, two hydrophobic interactions, one electrostatic interaction, and two Pi-cation interactions. The 5 ns molecular dynamics simulations confirmed that the structure of KLPGF with BACE1 was stable. Peptide KLPGF contacted the residues Lys321, Asp228, and Asn233 with stable hydrogen bonds. KLPGF may be a potential anti-BACE1 candidate.

The egg white-derived hexapeptide TNGIIR inhibits angiotensin-converting enzyme (ACE) activity in vitro. In this work, molecular docking revealed that TNGIIR established hydrogen bonds with the S1 (Ala 354), S2 (Gln 281, His 513, Tyr 520 and Lys 511) and S1′ (Glu 162) pockets of ACE. In addition, the potential antihypertensive effect of the oral administration of TNGIIR in spontaneously hypertensive rats (SHR) was investigated, as was the effect of this peptide on the mRNA expression of ACE and angiotensin type 1 (AT1) and type 2 (AT2) receptors in renal tissue. The oral administration of TNGIIR (2, 10 and 50 mg/kg) for up to four weeks did not reduce the blood pressure of SHR, in contrast to captopril (10 mg/kg, orally), but attenuated the mRNA expression of ACE and AT1 receptor (as did captopril). In contrast, both TNGIIR and captopril enhanced the expression of AT2 receptor mRNA. There was no change in the circulating concentration of fAng Ⅰ, 10 amino acids, but a slight decrease (about 10%) was seen in the concentration of circulating angiotensin Ⅱ with TNGIIR and captopril.