Charging free energies for charges placed in a quasi-spherical solute of radius 4 Å. Symbols represent FEP results for charges placed at different lattice points (x, 0, 0), where x spans the distance from 0 to 3.5 Åfrom the center of the sphere; results for x = 0.5 and x = 1 are omitted in the main figure for clarity, but included in the inset. Curves represent affine-response models derived from quadratic fitting over the interval −0.2e ⩽ q ⩽ +0.2e. Inset shows that the slopes of the charging free energies are practically identical for all charge positions at q = 0, indicating a nearly uniform static potential (mean value of 43.5 kJ/mol/e (thick line) with a standard deviation 1.3 kJ/mol/e) throughout the solute.