• Conventional QM/MM schemes, such as those combining TDDFT/TDA with the TIP3P fixed-charge and the EFP polarizable force fields for the water solvent, tend to systematically overestimate the vertical excitation energies by 0.1 eV or more for these two biochromphores, when compared against full-system TDDFT/TDA values. Such an overestimation is largely caused by the entanglement of both occupied and virtual orbitals of the chromophore to those of nearby solvent molecules.