Table A2.

Free energy differences of all substeps of the hydration free energy calculations with the CHARMM Drude force field in kcal/mol.

Molecule	$\mathbf{\Delta }{\mathit{G}}_{\mathit{gas}}$ a	$\mathbf{\Delta }{\mathit{G}}_{\mathbf{char}}$ b	Ovl c	$\mathbf{\Delta }{\mathit{G}}_{\mathbf{vdw}}$ d	Ovl c	$\mathbf{\Delta }{\mathit{G}}_{\mathbf{hyd}}$ e
water	$0.000$ ± $0.000$	$7.92$ ± $0.02$	52	$-2.15$ ± $0.02$	78	$-5.77$ ± $0.02$
methanol	$-11.646$ ± $0.003$	$-5.33$ ± $0.01$	57	$-1.42$ ± $0.03$	51	$-4.90$ ± $0.03$
ethanol	$-0.931$ ± $0.003$	$6.08$ ± $0.01$	51	$-2.36$ ± $0.05$	35	$-4.65$ ± $0.05$
methanethiol	$-2.528$ ± $0.000$	$-0.28$ ± $0.01$	83	$-1.21$ ± $0.03$	32	$-1.04$ ± $0.03$
acetamide	$104.139$ ± $0.004$	$119.42$ ± $0.01$	29	$-4.63$ ± $0.05$	35	$-10.64$ ± $0.06$
tetrahydrofuran	$0.648$ ± $0.002$	$4.61$ ± $0.02$	63	$-0.84$ ± $0.03$	20	$-3.12$ ± $0.04$
benzene	$-22.578$ ± $0.003$	$0.98$ ± $0.01$	76	$-22.20$ ± $0.05$	8	$-1.36$ ± $0.05$
phenol	$-16.280$ ± $0.010$	$11.82$ ± $0.02$	44	$-21.03$ ± $0.02$	7	$-7.07$ ± $0.03$
aniline	$-7.691$ ± $0.014$	$19.98$ ± $0.02$	43	$-21.54$ ± $0.05$	7	$-6.13$ ± $0.06$
ethane	$-3.769$ ± $0.001$	$-3.64$ ± $0.00$	95	$-2.29$ ± $0.02$	43	$2.16$ ± $0.02$
n-hexane	$-3.597$ ± $0.005$	$-2.39$ ± $0.01$	79	$-3.75$ ± $0.08$	7	$2.54$ ± $0.08$
cyclohexane	$-0.026$ ± $0.002$	$-0.09$ ± $0.00$	84	$-2.09$ ± $0.04$	7	$2.15$ ± $0.04$

^a Free energy difference associated with turning off all non-bonded interactions in the gas phase. ^b Free energy difference of uncharging the solute in aqueous solution. ^c Smallest BAR overlap integral of all $\lambda$-steps in % (cf. [133,161,197,198]). ^d Free energy difference of removing all Lennard–Jones interactions of the uncharged solute in aqueous solution. ^e Total hydration free energy (cf. Table 1).