Identification and molecular mechanism of a tri-peptide inhibitor targeting iNOS from duck embryo protein hydrolysates by experimental and bioinformatics studies

Abstract

Duck embryonic proteins are a promising source of food-derived functional peptides. Using a combination of experiments and bioinformatics approaches, a tri-peptide inhibitor YPW targeting iNOS was identified from duck embryo protein hydrolysates. Our results indicated that YPW could significantly inhibit LPS-induced NO generation in macrophages in a dose-dependent manner. YPW also significantly inhibited the expression of IL-6 and iNOS. Molecular simulations revealed that YPW could interact strongly with (iNOS) with a binding energy of -45.71 ± 17.75 kJ/mol. The stability of YPW-iNOS was maintained by the hydrogen bonds of amino acid residues Ile¹⁹⁵, Gly¹⁹⁶, Gly³⁶⁵, Glu³⁷¹, Asn³⁶⁴, and Trp³⁶⁶, and the hydrophobic interactions by Trp¹⁸⁸, Phe³⁶³, and Val³⁴⁶. In conclusion, our study provides a new idea for broadening the utilization of duck embryo proteins, and a strategy for the discovery of food-derived bioactive peptides.

Keywords: Inflammation; Molecular simulation; Simulated gastrointestinal digestion; iNOS.