hydration sites that are within the user-specified distance to any of
the ligand’s heavy atoms are added up to estimate its protein
desolvation free energy. A more positive value means a more favor-
able contribution to the protein–ligand binding free energy. The
predicted desolvation energies (ΔG,TΔS, andΔH) are displayed
in a new window, and the selection of displaced hydration sites is
highlighted in the PyMOL viewer (Fig.7b).
Binding site water displacement is a significant contribution, if
not the driving force, of protein–ligand binding. When a lead
compound is already known for a specific target, WATsite can be
useful in suggesting ligand modification in order to improve affinity
due to the displacement of hydration sites with unfavorable free
energies (seeNote 7).Fig. 7(a) Hydration site results predicted without the ligand. (b) The result of example case of HIV-1 protease
with bound ligand. The interfacial water molecules are selected
398 Ying Yang et al.