Table 3.

Effect of the buffer concentration on the binding affinity ($\Delta \Delta \Delta G_{\mathit{\text{bind}}}^{\Delta c_{\mathit{\text{buffer}}}}$) as a result from alchemically lowering the sodium chloride concentration in our simulations by about 10 – 20mM. The resulting absolute binding free energies of the systems with a concentration of 20 – 30mM and the standard deviations due to error propagation are shown in the rightmost column. The corresponding RMSE for the deprotonated guests is presented in the last row. All free energy differences are in kcal/mol.

Guest	$\Delta \Delta \Delta G_{\mathit{\text{bind}}}^{\Delta c_{\mathit{\text{buffer}}}}$	$\Delta G_{\mathit{\text{bind}}}^{20\mathit{\text{mM buffer}}}$
1	−0.7 ± 3.1	−9.8 ± 3.2
2	0.9 ± 1.7	−6.4 ± 1.8
3	2.4 ± 2.7	−2.9 ± 3.0
4	4.7 ± 2.2	−3.9 ± 2.3
5	−0.7 ± 1.6	−10.0 ± 1.8
6	1.1 ± 3.6	−7.9 ± 3.7
7	5.3 ± 3.0	−1.1 ± 3.1
RMSE		3.8