While this work was in progress, a newer version of Epik (Epik v. 7) came out and its accuracy on a portion of the Novartis set is also provided in Table . We also tested our models with the ionization center provided to the models (included in the input file) or not. In the latter case, our method will consider multiple ionization centers and ionization states. Whereas this benchmarking considers data splitting, the various sets used, and their similarities, it relies on one critical assumption: that the ionization centers in our datasets are correctly identified. Indeed, while some molecules may have multiple functional groups that could be ionized around the same pH, there is no mention of any experimental validation of these ionization center assignments. To compare further these models, we could for instance compare the predicted and experimentally proposed ionization site for each model's predictions. However, this approach might overlook false negative in molecules with identical functional groups occurring twice (e.g., symmetric diols) or even molecules presenting ionizations groups that are similarly acidic.