The results of the simulations described in this work allow us to conclude that the use of the QM/MM MD approaches considerably expands the repertoire of theoretical tools to model complex protein-ligand interaction. The treatment of protein-dioxygen complexes can hardly be handled at the level of molecular mechanics with conventional force fields. As shown in this work, quantum-based approaches may greatly assist in interpretation of crystallography data; in this case, accommodation of the oxygen molecule near the flavin moiety is improved. The QM/MM MD calculations enable us to speculate on the reaction mechanisms when analyzing trajectories near the reactant configurations.