Instead of ∆ML, direct ML/MM is a more efficient approach where QM is fully replaced by RMLPs. However, encoding the EE scheme with ML/MM is challenging since it is not immediately obvious how to polarize the ML region by the MM charges, unless the ML has a way to explicitly account for the external charge field. An easier alternative is to adopt a simpler ME scheme and therefore totally omit the mutual polarization between ML and MM region. For example, PhysNet ML/MM is developed and applied to simulate the double proton transfer of a hydrated formic acid dimer in water, where mutual polarization is expected to be small . Recently, the Xie group adopted a ME scheme with an EANN model in ML/MM to simulate a SN2 reaction in water . They further correct the ME result to EE using a weighted thermodynamic perturbation (wTP) scheme. Gastegger and coworkers developed FieldSchNet based on the original SchNet to model interactions of molecules with arbitrary external fields.