In QM/MM frameworks, the polarization contribution lowers the overall energy of the molecular system, but is partially counter balanced by an increase in the internal energy of the QM region due to the environment electric field, i.e., the distortion energy. We now explore the possibility of providing a estimation for the analogous distortion energy in a ML/MM framework. In Figure , we analyze the sum of the EE QM/MM coupling energy and the exact distortion energy (calculated as E sol QM -E vac QM , at the PBE/DZVP level of theory). In the left panel, the sum is compared with the the ML/MM coupling energy computed at the ME+P level, using MBIS charges derived from ωB97x/def2-TZVPP electron densities, and atom type-based atomic polarizabilities. In the right panel of the same Figure, we include the estimation of the distortion energy, E D ML , obtained according to equation ( ), with our best fit for the proportionality constant k AT (0.481 ± 0.002), with the subscript indicating the set of atomic polarizabilities used. The use of element-based polarizabilities shows comparable results (Figure ). Two main conclusions can be outlined from this analysis: the first one is that in terms of recovering a mathematical expression for the full energy (equation (1)), the ME+P approaches seems to lack a positive term; the second observation is that such missing contribution, which is necessarily related with the distortion energy, can be estimated from the polarization correction used in the ME+P approach. The distortion energy, across our data set, is approximately half the polarization energy (and of opposite sign), consistently with previous studies for QM/MM simulations of liquid water and small molecules in aqueous solution. Figure : Left-Correlation between the sum of the coupling energy given by the electrostatic embedding approach and the exact distortion energy (PBE/DZVP) and the coupling energy computed at the ME+P level, using MBIS charges derived from (ωB97x/def2-TZVPP), and atom type-based atomic polarizabilities. Right-Addition of the estimation of the distortion energy, with our best fit for the proportionality constant k AT = (0.481 ± 0.002). The dashed lines represent the identity. The color-scale represents the KDE of the probability density in units of (kcal/mol) -2 .