Figure 1:

Thermodynamic cycles for correcting solvation free energies (left) and ligand binding free energies (right) with QM “book-ending” corrections. It is assumed that the molecule/ion being solvated or the ligand that is binding is to be treated as the QM region, and the surrounding region that makes up the aqueous solution or aqeuous protein environment is modeled using an MM framework to give rise to the final QM/MM potential. In the case that an MM′ reference potential is used for the QM atoms as an intermediate, we designate the combined potential as MM′/MM, and for consistency, when the unmodified MM potential is used for both we designate the potential as MM/MM.