logP-Prediction Challenge timeframe: Nov 1, 2018 - Mar 22, 2019

SAMPL6 was originally announced as featuring a logD prediction challenge, but there were difficulties in the collection of experimental data. We were instead able to collect experimental neutral-compound log partition coefficients (logP) for a subset of the SAMPL6 pKa challenge compounds. Thus, these form the basis of SAMPL6 Part II -- a logP prediction challenge commencing immediately. We hope that the logP challenge will be useful in investigating sources of modeling errors that impact solvation, partition, and affinity predictions other than protonation state related errors that were prominent in SAMPL5 logD challenge.

This challenge consists of predicting the octanol-water partition coefficients (logP) of 11 small molecules that resemble fragments of small molecule protein kinase inhibitors. Our aim is to evaluate how well current models can capture the transfer free energy of small molecules between different solvent environments through blind predictions.

Participants are encouraged to submit articles evaluating their methods to the coming special issue or section of the Journal of Computer-Aided Molecular Design special issue targeting September 2019. The challenge will culminate with a joint D3R/SAMPL workshop.

Complete details on the SAMPL6 logP challenge are available in the SAMPL6 Github repository, where all information related to input structures and submission directions can be found: https://github.com/MobleyLab/SAMPL6

Experimental details

Experimental logP values were collected using potentiometric logP (pH-metric logP)[1-5] measurements with a Sirius T3 instrument by Mehtap Isik from the Chodera Lab at MSKCC with the support of the Pharmaceutical Sciences, MRL, Merck & Co., Inc, Preformulation Group, especially Dorothy Levorse, Timothy Rhodes, and Brad Sherborne. Three independent replicate measurements of log P in 1-octanol and water biphasic systems were performed at 25°C. Ionic strength adjusted water with 0.15 M KCl was used. More details on experimental data collection can be found in "Experimental details" section of logP challenge instructions on SAMPL6 GitHub Repo.

References

1. Comer, John, and Kin Tam. Lipophilicity Profiles: Theory and Measurement. Wiley-VCH: Zürich, Switzerland, 2001.
2. "Sirius T3 User Manual, v1.1." (Sirius Analytical Instruments Ltd, East Sussex, UK), 2008.
3. Avdeef, Alex. "PH-Metric Log P. Part 1. Difference Plots for Determining Ion-Pair Octanol-Water Partition Coefficients of Multiprotic Substances." Quantitative Structure-Activity Relationships 11, no. 4 (1992): 510-17.
4. Avdeef, Alex. "pH-Metric Log P. II: Refinement of Partition Coefficients and Ionization Constants of Multiprotic Substances." Journal of Pharmaceutical Sciences 82, no. 2 (1993): 183-90.
5. Slater, Bryan, Ann McCormack, Alex Avdeef, and John EA Comer. "Ph-Metric Log P. 4. Comparison of Partition Coefficients Determined by HPLC and Potentiometric Methods to Literature Values." Journal of Pharmaceutical Sciences 83, no. 9 (1994): 1280-83.