The inclusion of a polarizable MM region requires a self-consistent procedure to evaluate the total QM/MM energy of a system in a given state s. At a single step p within this self-consistent procedure, first a QM level calculation (DFT for the ground state s = g , DFT+GW -BSE for electron-hole excited s = x states) is performed in the electric field generated by the total moments in the MM region. The total energy of the QM region in state s is then given by Eq. ( ), and excitation energies are obtained from it and the energy of the classical region via "∆-QM/MM-SCF" formulations as total energy differences according to Eq. ( ). In Figure this is indicated by the three different "routes" that the calculation can take through the algorithm: Route 1 corresponds to the reference ground state calculation in which the MM region has responded to the plain DFT density of the QM region; in route 2 the external polar field the MM enacts on the QM region is determined as a response from the quasiparticle density Eq. (90) (GW/MM); and route 3 is used to get the total QM/MM energy in which the density in the QM region is determined according to Eq. ( ).