Thermodynamic properties. Thermodynamic quantities E sw , E ww , TS trans , TS orient and ∆G solv at each hydration site were calculated by summing all the grid points within a radius r of 1.4 Å around it, and Gaussian-weighted by their distance using a σ value calculated as: σ = r/3. The Gaussianweighting ensured that voxels in close proximity of the hydration site centers had more weight than distant ones. GIST grid energy values were converted to kcal/mol by multiplying them by the voxel volume (0.125 Å 3 ).