Figure 1.

The various thermodynamic cycles employed in the ssEA, NBB4, and NBB13 methods to calculate binding free energies at the QM level. The cycles apply for the ligand simulated both with and without the host, giving either $\Delta G_{\text{bound}}^{\text{QM}}$ or $\Delta G_{\text{free}}^{\text{QM}}$ in eq. (2) (indicated by $\Delta G_s^{\text{QM}}$ in the figures). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]