Fig. 6. A single, global minimum conformation can be used to calculate tautomeric free energy differences in solution without loss of accuracy. These results are based on the calculations with B3LYP/aug-cc-pVTZ/B3LYP/6-31G(d)/SMD. (A) shows the tautomeric free energy difference ΔtGcalcsolv obtained with multiple minima (m.m.) plotted against the global, single minimum (s.m.) tautomeric free energy difference ΔtGcalcsolv. (B) shows the KDE and histogram of the difference between s.m. ΔtGcalcsolv and m.m. ΔtGcalcsolv. The comparison indicates that there is little benefit using multiple minimum structures over a single, global minimum considering the high costs of the former. Comparing two estimated properties we use root mean squared deviation (RMSD) and mean absolute deviation (MAD) instead of error.
