Residues surrounding the ligand, containing any atom within the cut-off distance, are classified as the low-level QM2 region of the ONIOM method (Figure ). All the remaining residues of the receptor comprise the MM region. For the QM region, electronic structure methods such as the Hartree-Fock (HF), density functional theory (DFT), second-order Møller-Plesset perturbation (MP2), and coupled-cluster (CC) theories may be employed .