is the electron density. Here, the MM q i charges are fixed parameters and the electric field generated by them is accounted for the optimization of the electron density ρ(r). An im-proved approximation called polarizable embedding incorporates the polarization within the MM region; however, while several schemes have been proposed, the resulting improvements have proven to be modest. On the other hand, the so called mechanical embedding (ME) approach computes the QM/MM electrostatic energy by the Coulombic interaction of point charges centered in each atom, i.e., atomic partial charges: