Abstract

In a unique collaboration between Simulations Plus and several industrial partners, we were able to develop a new version 11.0 of the previously published1 in silico pKa model, S+pKa, with considerably improved prediction accuracy. The model’s training set was vastly expanded by large amounts of experimental data obtained from F. Hoffmann-La Roche AG, Genentech Inc., and the Crop Science division of Bayer AG. The previous v7.0 of S+pKa was trained on data from public sources and the Pharmaceutical division of Bayer AG. The model has shown dramatic improvements in predictive accuracy when externally validated on three new contributor compound sets. Less expected was v11.0’s improvement in prediction on new compounds developed at Bayer Pharma after v7.0 was released (2013-2023), even without contributing additional data to v11.0. We illustrate chemical space coverage by chemistries encountered in the five domains, public and industrial, outline model construction, and discuss factors contributing to model’s success.

By Robert Fraczkiewicz, Huy Quoc Nguyen, Newton Wu, Nina Kausch-Busies, Sergio Grimbs, Kai Sommer, Antonius ter Laak, Judith Günther, Björn Wagner, Michael Reutlinger