Homology Modeling of Human Tyrosinase

The protein structure of the target enzyme human Tyrosinase (hTYR) has no resolved X-ray crystallographic or cryo-EM structure available in the protein databank yet. Therefore, the amino acid sequence of this enzyme was taken from the UniProt database with sequence ID-P14679 and a new protein structure of this enzyme was homology modelled by utilizing the SWISS-MODEL^{51 (link)} server. The template (used) for modelling this structure, was hTYRP1 (human tyrosinase-related protein-1) with PDB ID-5M8L⁵² as this enzyme showed the highest homology with the human tyrosinase. As the hTYRP1 contains the Zn⁺⁺ as active catalytic atoms and the hTYR contains the Cu⁺⁺ ions utilizing the MOE v2022 software, the copper ions were modelled into the prepared homology modelled hTYR enzyme active site. The protein structure was further optimized via the protein preparation function in the MOE v2022. The structures of ligands were prepared in ChemDraw professional v16.0 and then it was imported to MOE for further optimization. After that, the ligands were docked using the online version of AutodockVina (v1.2.3) known as Webina^{53–55 (link)} by creating a box with XYZ dimensions of 22 Å and around the catalytic hub of the modelled tyrosinase enzyme with the grid coordinates of the docking site centered at X = 32.154, Y = 140.176, Z = 215.585. The molecular interaction and conformational analysis of the ligand–protein complexes were performed in Biovia DS v2017 software.