Figure 2.

Cartoon depicting the spatial decomposition of the IST integral equations introduced in equations 11 to 13. The net “surf” term is the difference in the free energetic cost of the fluid reorganizing its configuration around the surface of the ligand cavity when the cavity is bound to the protein versus free in solution, and the net “N_w solv” term corresponds to the difference in the local IST integral free energy of the N_w water occupying the active site of the protein versus the IST integral free energy of the same N_w water molecules in the bulk fluid.