Table 6.

RMS pK_aerrors compared across calculations

	Null	FD ɛp = 20	FD VdW SA	DH	FD/DH	FD/DH no Δ(TΔS)QWAT	FD/DH no Hmove	FD
110 gps	0.77	0.78	1.06	0.58	0.79	1.02	1.11	2.10
117 gps	1.24	1.25	1.46	1.18	0.86	1.25	1.16	2.06

Sets of 110 and 117 groups explained in Materials and Methods. All calculations include polar hydrogen optimization except for the column labeled “no Hmove”. FD/DH schemes include hydration modification for the FD component except for the “no Δ(TΔS)_QWAT” column. Of the FD calculations, only the FD column uses this modification. It is not appropriate for either ɛ_p = 20 or VdW solvent accessibility schemes, which are closer to DH in terms of water domination. FD/DH calculations were made with VdW_tol = 1.4 Å. Null refers to model compound pK_as in place of calculated values. RMS pK_a error = sqrt {[∑(pK_a^expl−pK_a^calc)²]/N}, where the sum runs over the N ionizable groups with measured pK_as.