In the electrostatic embedding scheme, which is commonly used when applying QM/MM to enzymatic reactions, the electron density of subsystem A is polarized by the MM point charges of subsystem B. The MM point charges are included in the QM Hamiltonian 4 to compute the interaction between the electron density ρ A (r) of subsystem A and the electrostatic potential V B (r) derived from the point charges of subsystem B,