In silico identification and mechanistic evaluation of novel tyrosinase inhibitory peptides derived from coconut proteins

Abstract

Globulin proteins of coconut were in silico hydrolysis by proteinases for screening potential tyrosinase inhibitory peptides, of which their inhibitory mechanisms were investigated through molecular docking and molecular dynamics simulations. First, the coconut globulin was in silico hydrolyzed using the PeptideCutter online enzymatic digestion software. Second, prediction of toxicity of the hydrolyzed peptides was performed using ToxinPred, while Innovagen was employed for the determination of their water solubility. Third, the peptides were docked into tyrosinase to determine the binding site and its binding strength. Fourth, the inhibitory activity of the peptides against tyrosinase was experimentally validated. Finally, the inhibitory mechanism was investigated by molecular dynamics simulations and isothermal titration calorimetry. The results showed that the peptide Asp-Gly-Glu (DGE) exhibited an inhibitory effect on tyrosinase, with an IC50 value of 9.58 ± 0.01 mM. Moreover, His61, His296, Asn260, and Arg268 were the crucial amino acid residues enabling the binding of DGE to the pocket of tyrosinase. The present study demonstrates that the peptide DGE can be used as a tyrosinase inhibitor to prevent and ameliorate hyperpigmentation and other tyrosinase-related problems. This study provides a theoretical basis for the development of novel safe and effective tyrosinase inhibitory peptides.