It is well established that tautomerism depends on a number of factors (e.g., pH, temperature, and solvent) and experimentally identifying the dominant tautomeric form for each compound across large databases is typically not practical. High-level quantum chemical calculations are the next best alternative to experimental determination. However, these calculations are not feasible for large number of structures due to high computational cost, not to speak of difficulties of accurately representing all environmental conditions in such runs. Instead, rule-based cheminformatics approaches are used in practice. These approaches are not derived from first principles; rather, they are based on predefined rules and empirical scoring functions.