Name
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 ($$K_{\rm ow}$$), 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 $$\hbox {p}{K}_{{\rm a}}$$ 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. |
Year | DOI | Venue |
|---|---|---|
2020 | 10.1007/s10822-019-00271-3 | Journal of Computer-Aided Molecular Design |
Keywords | DocType | Volume |
Octanol–water partition coefficient, log P
, Blind prediction challenge, SAMPL, Kinase inhibitor fragments, 4-Aminoquinazoline, Potentiometric log P measurement | Journal | 34 |
Issue | ISSN | Citations |
4 | 0920-654X | 1 |
PageRank | References | Authors |
0.35 | 0 | 5 |
Name | Order | Citations | PageRank |
|---|---|---|---|
| Mehtap Işık | 1 | 3 | 1.06 |
| Dorothy Levorse | 2 | 1 | 0.35 |
| David L. Mobley | 3 | 219 | 20.01 |
| Timothy Rhodes | 4 | 2 | 0.70 |
| John D Chodera | 5 | 46 | 7.89 |