TABLE IV.

Hydration free energies (in kcal/mol) from QM/MM-NBB and MESS-QM/MM-NBB calculations using BLYP or M06-2X functionals and the 6-31G* basis set. QM/MM-NBB results without including polarization energy (ΔE₁ only) are also listed for comparision. For each functional, MSE and RMSE values are computed against full QM/MM-NBB results.

molecule	BLYP			M06-2X
	Full QM/MM	MESS-E-QM/MM	ΔE1 only	Full QM/MM	MESS-E-QM/MM	ΔE1 only
water	−7.10±0.14	−7.08±0.14	−4.99±0.14	−8.42±0.15	−8.37±0.15	−6.15±0.14
methanol	−3.84±0.05	−3.81±0.06	−2.06±0.09	−5.08±0.04	−5.00±0.04	−3.00±0.09
ethanol	−3.89±0.10	−3.85±0.11	−1.99±0.10	−5.13±0.13	−5.10±0.14	−2.94±0.10
methanethiol	−3.10±0.32	−3.09±0.33	−1.81±0.14	−3.28±0.34	−3.22±0.34	−1.95±0.14
acetamide	−11.68±0.30	−11.19±0.21	−6.61±0.21	−13.62±0.34	−13.37±0.27	−8.12±0.20
tetrahydrofuran	−3.29±0.07	−3.29±0.08	−1.03±0.09	−4.71±0.09	−4.68±0.10	−2.02±0.07
benzene	−0.59±0.12	−0.56±0.12	0.34±0.12	−1.39±0.12	−1.35±0.12	−0.31±0.12
phenol	−6.03±0.13	−5.92±0.14	−3.60±0.16	−7.67±0.15	−7.50±0.13	−4.92±0.15
aniline	−6.67±0.31	−6.82±0.34	−4.36±0.19	−8.29±0.33	−8.26±0.32	−5.75±0.19
ethane	2.04±0.12	2.04±0.12	2.34±0.12	2.02±0.12	2.02±0.12	2.32±0.12
hexane	2.19±0.26	2.16±0.26	2.93±0.27	2.15±0.26	2.12±0.26	2.89±0.27
cyclohexane	1.03±0.10	1.03±0.10	1.69±0.09	1.01±0.10	1.00±0.10	1.67±0.10
MSE		0.05	1.81		0.06	2.01
RMSE		0.15	2.18		0.10	2.41