. Author manuscript; available in PMC: 2020 Aug 13.

Published in final edited form as: J Chem Theory Comput. 2019 Jul 2;15(8):4632–4645. doi: 10.1021/acs.jctc.9b00084

Table 3.

IEA compared to full free energy correction (Fig. 2) as applied to the computation of the solvation free energy ΔA_solv of bis-2-chloroethylether (2CLE). All free energies in kcal/mol. The experimental solvation free energy is –4.23 kcal/mol.⁹⁵

	full^b	IEA^c
$Δ A_{g a s p}^{C 36 \to D F T B 3}$ ^a	-27.34±0.20
$Δ A_{a q}^{C 36 \to D F T B 3}$ ^a	-27.54±0.53
$Δ A_{c o r r}^{C 36 \to D F T B 3}$ ^d	-0.20±0.57	1.73±0.26
$Δ A_{s o l v}^{C 36}$ ^e	-3.26±0.08	-3.26±0.08
$Δ A_{s o l v}^{D F T B 3 / M M}$ ^f	-3.46±0.57	-1.53±0.27
$Δ A_{g a s p}^{G A A M P \to D F T B 3}$ ^a	-33.55±0.13
$Δ A_{a q}^{G A A M P \to D F T B 3}$ ^a	-35.79±0.04
$Δ A_{c o r r}^{G A A M P \to D F T B 3}$ ^d	-2.24±0.14	-0.88±0.20
$Δ A_{s o l v}^{G A A M P}$ ^e	-0.81±0.03	-0.81±0.03
$Δ A_{s o l v}^{D F T B 3 / M M}$ ^f	-3.05±0.14	-1.69±0.20

For better readability, free energies listed in the table are offset by +12,200 kcal/mol.

Corrections ΔA^MM→DFTB3 (MM is C36 or GAAMP) computed separately in gas phase and in solution, cf. Fig. 2. Results as reported were computed using non-equilibrium work methods, specifically Crook’s equation.

Correction $Δ A_{a q, inter}^{M M \to D F T B 3}$ (MM is C36 or GAAMP) computed according to the IEA; cf. Eq. 4

Eq. 9, MM is C36 or GAAMP.

Classical solvation free energy for 2CLE computed using the C36 or GAAMP force field parameters for the solute. This corresponds to the horizontal arrow at the bottom of Fig 2. For details of the computational protocol see SI.

Solvation free energy for 2CLE corrected to the DFTB3/MM level of theory: $Δ A_{s o l v}^{D F T B 3 / M M} = Δ A_{s o l v}^{M M} + Δ A_{c o r r}^{M M \to D F T B 3},$ where MM is C36 or GAAMP.