In this expression, R ML and R MM represent the nuclear coordinates of atoms in the ML and MM region. E vac ML is the in vacuo energy for the ML region, E D ML represents the distortion energy that accounts for the cost of polarizing the ML region, E MM is the energy of the MM region, and E ML/MM denotes the interaction energy between the ML and MM subsystems. This interaction energy includes a non-electrostatic contribution utilizing predetermined Lennard-Jones parameters for ML atoms, alongside an electrostatic component, E elec ML/MM , calculated as follows: