The energy of the QM region, E QM (A), is obtained from a quantum-chemical calculation of the corresponding subsystem A. To allow for covalent bonds to cross the boundary between the QM and MM regions, the QM subsystem is usually saturated using capping atoms. The energy of the MM region, E MM (B), is calculated using a classical force field and contains the usual bonding and non-bonding force-field energy contributions. Finally, the interaction energy E int (A, B) contains both electrostatic interactions [E int,el (A)] and non-electrostatic interactions [E int,ne (A, B)] between the two subsystems.