for a few examples our algorithm resulted in more specific SMARTS patterns matching the DG. For example, Figure shows the result from Tomberg et al. , which does not include the carbonyl oxygen in the SMARTS pattern match although the pattern marked in red in Figure is part of the database. This example also highlights that in some cases the QM results are quite sensitive towards small structural changes. Another example that highlights the difficulties in prioritizing the SMARTS patterns is shown in Figure . The site marked with an arrow has three matching SMARTS patterns, which are sorted from left to right in accordance with our priority rules. The first two patterns result in quite different DG strengths, whereas the first and last patterns have similar DG strengths. In this case, the first pattern is really important as the assigned DG strength would otherwise have been completely different than intended.