Abstract
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
Combinatorial Chemistry & High Throughput Screening
Title: Predicting the pKa of Small Molecules
Volume: 14 Issue: 5
Author(s): Matthias Rupp, Robert Korner and Igor V. Tetko
Affiliation:
Keywords: pKa, acid dissociation constant, QSPR, quantitative structure-property relationships, molecular representations, weak acid, Brønsted-Lowry theory, multiprotic, amphiprotic, compound
Abstract: 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.
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Cite this article as:
Rupp Matthias, Korner Robert and V. Tetko Igor, Predicting the pKa of Small Molecules, Combinatorial Chemistry & High Throughput Screening 2011; 14 (5) . https://dx.doi.org/10.2174/138620711795508403
DOI https://dx.doi.org/10.2174/138620711795508403 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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