TABLE VI.

Hydration free energies in kcal/mol from F-MM-TIP3P (MM simulations with frozen-gas-phase-geometry SAMPL4 solute molecules and TIP3P water molecules) and MESS-E-QM/MM-NBB calculations using five density functionals and the 6–31G* basis set. MSE’ and RMSE’ are computed for molecules 2 through 21.

molecule	Expt	F-MM-TIP3P	MESS-E-QMMM-NBB
			BLYP	B3LYP	PBE0	M06-2X	ωB97X-D
1	−23.62	−18.75±0.19	−18.45±0.23	−20.35±0.31	−21.19±0.37	−22.04±0.42	−21.82±0.40
2	−2.49	−3.69±0.11	−3.18±0.13	−3.91±0.14	−4.45±0.16	−4.27±0.13	−4.51±0.16
3	−4.78	−5.42±0.03	−6.03±0.03	−6.77±0.04	−7.41±0.07	−7.47±0.08	−7.53±0.07
4	−4.45	−4.79±0.23	−5.55±0.24	−6.29±0.24	−7.06±0.26	−7.09±0.25	−7.10±0.26
5	−5.33	−7.04±0.20	−4.45±0.48	−5.56±0.46	−6.25±0.50	−6.51±0.46	−6.57±0.47
6	−5.26	−9.13±0.08	−7.56±0.45	−8.91±0.46	−9.99±0.50	−10.37±0.51	−10.44±0.54
9	−8.24	−12.26±0.09	−9.38±0.92	−10.12±0.87	−10.14±0.94	−10.27±0.91	−10.49±0.88
10	−6.24	−7.63±0.24	−5.30±0.18	−6.08±0.19	−6.35±0.19	−6.70±0.19	−6.71±0.18
11	−7.78	−9.10±0.14	−7.95±0.48	−8.82±0.35	−8.89±0.37	−9.10±0.38	−9.30±0.36
12	−3.75	−5.34±0.16	−4.23±0.18	−5.00±0.20	−5.34±0.20	−5.25±0.20	−5.65±0.20
13	−4.44	−5.38±0.19	−5.04±0.24	−5.68±0.22	−6.41±0.21	−6.52±0.21	−6.54±0.20
14	−4.09	−6.54±0.32	−4.63±0.36	−5.24±0.37	−5.56±0.42	−5.29±0.36	−5.63±0.37
15	−4.48	−4.03±0.17	−5.95±0.32	−6.78±0.35	−6.87±0.28	−6.53±0.30	−7.10±0.33
16	−3.20	−2.87±0.25	−3.84±0.28	−4.49±0.29	−4.86±0.29	−5.07±0.30	−5.05±0.30
17	−2.53	−4.57±0.16	−3.62±0.20	−4.32±0.22	−4.54±0.21	−4.49±0.21	−4.75±0.23
19	−3.78	−2.93±0.15	−3.51±0.25	−4.17±0.23	−5.23±0.22	−5.05±0.21	−5.12±0.22
20	−2.78	−2.21±0.30	−2.23±0.30	−2.88±0.30	−3.79±0.30	−3.64±0.30	−3.67±0.30
21	−7.63	−7.73±0.23	−8.29±0.32	−9.19±0.36	−9.95±0.39	−9.95±0.38	−10.12±0.37
22	−6.78	−4.97±0.14	−8.09±0.20	−9.06±0.20	−9.99±0.20	−10.09±0.18	−10.06±0.19
23	−9.34	−4.18±0.13	−3.98±0.19	−5.10±0.23	−6.38±0.27	−6.33±0.27	−6.43±0.27
24	−7.43	−5.00±0.32	−5.03±0.24	−6.00±0.24	−7.62±0.29	−7.48±0.28	−7.44±0.27
MSE		−0.24	0.10	−0.78	−1.42	−1.48	−1.60
RMSE		2.33	1.95	1.96	2.18	2.18	2.30
R2		0.72	0.82	0.84	0.87	0.87	0.86
MSE’		−1.14	−0.55	−1.35	−1.87	−1.90	−2.06
RMSE’		1.79	1.02	1.63	2.10	2.15	2.29