Following the line in which a ML method would provide a set of {q vac j } atomic charges onthe-fly, one could evaluate equation ( ) to obtain an estimation at the ME level (E ME ML/MM ). Similarly, one could use equation (6) to estimate the polarization energy, and therefore an estimation of the electrostatic coupling energy at the ME+P level (E ME+P ML/MM ), evaluating equation ( ). Finally, one can estimate the distortion energy associated with the ML subsystem with equation (7).