Figure 9.

This cartoon depicts the thermodynamic cycle and transformation used for the absolute binding free energy calculations from Figure 2. We take ΔG_bind = ΔG_solv – ΔG_site – ΔG_restraints. In its weakly and noninteracting state, the ligand is free to leave the binding site. We use orientational Boresch-style restraints to reduce the phase space that must be sampled.⁶⁴