Molecular dynamics simulations of laccase immobilized by 4-aminothiophenol (4-ATP) were performed to understand the origin of the enhanced catalytic activity at 350 K of laccase immobilized by self-assembled monolayers. The simulation showed that laccase was stabilized by bonding with 4-ATP. In addition, docking simulation of 2,6-dimethoxyphenol (DMP) to laccase revealed that the hydrophobic interaction energy was increased by bonding with 4-ATP. The variations of docking site size were minor considering the dimensions of DMP molecule. Therefore, it is suggested that the enhanced catalytic activity of laccase with 4-ATP is attributed to the high hydrophobic interaction energy between laccase and DMP.