Figure 1.

Shown in the figure is path for the free energy computation accordinng to the alchemical DDM with restraining potentials. $L_{\mathrm{aq}}^{\mathrm{c}}$ denotes the configuration restricted ligand in bulk solvent. $L_{\mathrm{vac}}^{\mathrm{c}}$ denotes the non-interacting ligand with configurational restraint. $L_{\mathrm{vac}}^{\mathrm{c},\mathrm{r}}$ denotes the non-interacting ligand with both configurational and rotational restraints. The spring represents the translational restraint potential. See reference 34 for a complete theoretical formulation.