Octanol-water partition coefficient measurements for the SAMPL6 blind prediction challenge Journal Article
| Authors: | Işık, M.; Levorse, D.; Mobley, D. L.; Rhodes, T.; Chodera, J. D. |
| Article Title: | Octanol-water partition coefficient measurements for the SAMPL6 blind prediction challenge |
| Abstract: | Partition coefficients describe the equilibrium partitioning of a single, defined charge state of a solute between two liquid phases in contact, typically a neutral solute. Octanol–water partition coefficients (Kow), or their logarithms (log P), are frequently used as a measure of lipophilicity in drug discovery. The partition coefficient is a physicochemical property that captures the thermodynamics of relative solvation between aqueous and nonpolar phases, and therefore provides an excellent test for physics-based computational models that predict properties of pharmaceutical relevance such as protein-ligand binding affinities or hydration/solvation free energies. The SAMPL6 Part II octanol–water partition coefficient prediction challenge used a subset of kinase inhibitor fragment-like compounds from the SAMPL6 p Ka prediction challenge in a blind experimental benchmark. Following experimental data collection, the partition coefficient dataset was kept blinded until all predictions were collected from participating computational chemistry groups. A total of 91 submissions were received from 27 participating research groups. This paper presents the octanol–water log P dataset for this SAMPL6 Part II partition coefficient challenge, which consisted of 11 compounds (six 4-aminoquinazolines, two benzimidazole, one pyrazolo[3,4-d]pyrimidine, one pyridine, one 2-oxoquinoline substructure containing compounds) with log P values in the range of 1.95–4.09. We describe the potentiometric log P measurement protocol used to collect this dataset using a Sirius T3, discuss the limitations of this experimental approach, and share suggestions for future log P data collection efforts for the evaluation of computational methods. © 2019, Springer Nature Switzerland AG. |
| Keywords: | ph; thermodynamics; water; computer model; ligand binding; phosphotransferase inhibitor; benzimidazole derivative; physical chemistry; pyrimidine; partition coefficient; cheminformatics; octanol; priority journal; article; ampholyte; sampl; solvation; pyridine; voltammetry; blind prediction challenge; log p; octanol–water partition coefficient; 4-aminoquinazoline; kinase inhibitor fragments; potentiometric log p measurement; potentiometric titration |
| Journal Title: | Journal of Computer-Aided Molecular Design |
| Volume: | 34 |
| Issue: | 4 |
| ISSN: | 0920-654X |
| Publisher: | Springer |
| Date Published: | 2020-04-01 |
| Start Page: | 405 |
| End Page: | 420 |
| Language: | English |
| DOI: | 10.1007/s10822-019-00271-3 |
| PUBMED: | 31858363 |
| PROVIDER: | scopus |
| PMCID: | PMC7301889 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 May 2020 -- Source: Scopus |
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