Theoretical studies of arbutin, glutathione, and sea cucumber extracts as inhibitors of tyrosinase.

Tyrosinase is a crucial enzyme targeted for the development of various skin-whitening agents due to its role in regulating key steps in melanin production. Despite the significance of human tyrosinase (hTYR), its crystal structure remains unresolved, hindering the development of specific inhibitors. Researchers frequently use mushroom tyrosinase (mTYR) to evaluate the inhibition capabilities of compounds, but the structural differences between hTYR and mTYR present considerable challenges in accurately developing hTYR-specific inhibitors. For instance, compounds like kojic acid show promising inhibitory effects but face limitations due to cytotoxicity or allergic reactions. This study aims to utilize the AlphaFold-predicted structure of hTYR to provide insights for developing specific inhibitors by comparing it with mTYR. We utilized natural tyrosinase inhibitors reported in the literature for molecular docking and molecular dynamic simulations to examine their binding modes with mTYR and hTYR. Through the analysis of these binding interactions and dynamic behaviors, we intend to identify residues that significantly enhance affinity, assess reliable binding modes, and offer essential insights for the development of effective hTYR inhibitors.