Figure 1.

Cartoon depicting the relationship between $\mathrm{\Delta }{\langle {\text{W}}_{\text{PL}}\rangle }_{\text{P},\text{L};\text{PL}}^{\text{chrg}}$ and <U_P-L>_PL. $\mathrm{\Delta }{\langle {\text{W}}_{\text{PL}}\rangle }_{\text{P},\text{L};\text{PL}}^{\text{chrg}}$ is the free energy difference in turning on the attractive and electronic interaction between the ligand and the solvent in the bulk water (left) versus in the active site of protein (right), which is the interaction between the ligand and the solvent that would be excluded by the protein (depicted by dashed line on the left). <U_P-L>_PL is the interaction energy between the ligand and the protein in the complex (right). For complementary ligands binding to the protein receptor, the two terms would be expected to be of similar magnitude.