Insight into the Inhibitory Activities of Diverse Ligands for Tyrosinase Using Molecular and Structure-based Features

Tyrosinase, which is closely related to blacking fruit and vegetable, larva development and abnormal deposition of melanin inside human skin, distribute broadly in cells of animal, plant and microorganism. Harmless inhibitors of tyrosinase can be used for lengthening storing time of fruits and vegetables, resisting insects in agriculture and cuing stain. Exploration of common pharmacophores of tyrosinase inhibitors provides ways to understand the inhibitory mechanism and design safe inhibitors. In this study, structure-based features based on MM-PBSA method and binding free energy computation were combined with molecular features to setup a descriptive relationship between tyrosinase inhibitory active and molecular structure for 46 diverse ligands. Monte Carlo and random Forest algorithms were used to build regression model for multiple variable and case. Explicit models using Monte Carlo provided 0.66, and implicit models using Random Forest afforded 0.92 for Pearson correlation coefficients (R2). By analyzing the common structure of 46 inhibitors, we found that the hydroxyl in ring B of flavonoid could binding to active site of tyrosinase directly and exhibit strong inhibitory active. Other structure similar with flavonoid could inhibit tyrosinase as well. The inhibitors including 2,4-dihydroxyphenol group at one end of molecular structure show up strongest inhibitory force.