A correct prediction is one where all the experimentally observed sites are predicted (with a green dot) by at least one of the tautomers, so one worry is that the high cutoff simply leads to a large number of tautomers each with a different site being predicted as most reactive. However, an analysis of the data (Fig. ) shows that 91% of the molecules in our data set have only have one or two tautomers, even for a cutoff of 15 kcal/mol. This statistic is reflected in the 11 molecules for which the predictions improve using a cutoff of 15 kcal/mol (Fig. ). Of these 11 molecules only two have more than two tautomers and in all cases the increase in accuracy is a result of only one new position being predicted as most reactive (Fig. ). Thus, RegioSQM20 uses a 15 kcal/mol cutoff for tautomers, which increases the number of correct predictions to 496 molecules (Table ) and the median and total CPU time to 49 seconds and 17 hours, respectively.