Predicting the pKa of Small Molecules
Matthias Rupp, Robert Körner, Igor V. Tetko · Combinatorial Chemistry & High Throughput Screening · 2011
The biopharmaceutical profile of a compound depends directly on the dissociation constants of its acidic and basic groups, commonly expressed as the negative decadic logarithm pKa of the acid dissociation constant (Ka). We survey the literature on computational methods to predict the pKa of small molecules. In this, we address data availability (used data sets, data quality, proprietary versus public data), molecular representations (quantum mechanics, descriptors, structured representations), prediction methods (approaches, implementations), as well as pKa-specific issues such as mono- and multiprotic compounds. We discuss advantages, problems, recent progress, and challenges in the field. Keywords: pKa, acid dissociation constant, QSPR, quantitative structure-property relationships, molecular representations, weak acid, Brønsted-Lowry theory, multiprotic, amphiprotic, compound