Figure 2.

Shown in the figure is path for the free energy computation using a PMF-based method with restraining potentials. $L_{\mathrm{aq}}^{\mathrm{c}}$ denotes the configuration restricted ligand in bulk solvent. $L_{\mathrm{aq}}^{\mathrm{c},\mathrm{o}}$ denotes the ligand with both configuration and orientation restraints. $L_{\mathrm{aq}}^{\mathrm{c},\mathrm{o},\mathrm{a}}$ denotes the ligand in the bulk with all configurational, orientational and axial restraint potentials. $\Delta G_{\mathrm{a}}^{\text{bulk}}$ is related to S* in Eq (9). ΔG^bulk→site is related to I* in Eq (9). See reference 49 for a complete theoretical formulation.