Mutation on Enhanced Cyan Fluorescent Protein (ECFP) has been investigated by means of a hybrid quantum mechanics and molecular mechanics (QM/MM) approach. A simple model, which represents the electronic response of the surroundings (ERS) by a polarizable continuum characterized by the relative dielectric constant extrapolated to infinite frequency, is used. For all mutations, this method (QM/MM+ERS) reproduces the experimental trend (shift) and is in correct agreement with experimental maximum absorption wavelength (between -10 and +10 nm). The effect of the ECFP on the optical properties is analyzed and decomposed into three major contributions (geometric deformation, electrostatic polarization and electronic response). It is shown that these three contributions have similar magnitude and one cannot neglect one with respect to the others. In addition, these contributions differ greatly from one chromophore to another showing that the same protein framework acts differently on different chromophores.