Fig. 7. Independent of the level of theory, thermochemistry corrections introduce a mean absolute deviation (MAD) of 0.9 kcal mol−1. ANI-1ccx is used for the calculation of tautomeric free energy differences in vacuum ΔtGcalcvac using alchemical relative free energy (AFE) calculations and single point energy calculations on multiple minimum conformations and thermochemistry corrections based on the RRHO approximation. (A) shows a scatter plot between the two approaches and (B) the KDE and histogram of the difference between the two approaches. Error bars are shown in red on the alchemical relative free energy estimates, these were obtained from the MBAR estimate of the relative free energy (see Methods section). Comparing two estimated properties we use root mean squared deviation (RMSD) and mean absolute deviation (MAD) instead of RMSE/MAE.
