Comments on the article "Evaluation of pK(a) estimation methods on 211 druglike compounds".

The recent article "Evaluation of pK(a) Estimation Methods on 211 Druglike Compounds" ( Manchester, J.; et al. J.

Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution.

Generating the appropriate protonation states of drug-like molecules in solution is important for success in both ligand- and structure-based virtual screening. Screening collections of millions of compounds requires a method for determining tautomers and their energies that is sufficiently rapid, accurate, and comprehensive. To maximise enrichment, the lowest energy tautomers must be determined from heterogeneous input, without over-enumerating unfavourable states.