Octanol-water partition coefficient measurements for the SAMPL6 Blind Prediction Challenge


Mehtap Işık, Dorothy Levorse, David L. Mobley, Timothy Rhodes, and John D. Chodera.
Preprint ahead of publication.
[bioRxiv] [data] [GitHub]

We describe the design and data collection (and associated challenges) for the SAMPL6 part II logP octanol-water blind prediction challenge, where the goal was to benchmark the accuracy of force fields for druglike molecules (here, molecules resembling kinase inhibitors).

pKa measurements for the SAMPL6 prediction challenge for a set of kinase inhibitor-like fragments

Mehtap Işık, Dorothy Levorse, Ariën S. Rustenburg, Ikenna E. Ndukwe, Heather Wang , Xiao Wang , Mikhail Reibarkh , Gary E. Martin , Alexey A. Makarov , David L. Mobley, Timothy Rhodes*, John D. Chodera*.
* co-corresponding authors
Journal of Computer-Aided Molecular Design special issue on SAMPL6 32:1117, 2018.
[DOI] [PDF] [bioRxiv] [Supplementary Tables and Figures] [Supplementary Data (includes Sirius T3 reports on all measurements)]

The SAMPL5 blind challenge exercises identified neglect of protonation state effects as a major accuracy-limiting factor in physical modeling of biomolecular interactions. In this study, we report the experimental measurements behind a SAMPL6 blind challenges in which we assess the ability of community codes to predict small molecule pKas for small molecule resembling fragments of selective kinase inhibitors.

Quantitative self-assembly prediction yields targeted nanomedicines

Yosi ShamayJanki Shah, Mehtap Işık, Aviram MizrachiJosef LeiboldDarjus F. TschaharganehDaniel RoxburyJanuka Budhathoki-UpretyKarla NawalyJames L. SugarmanEmily BautMichelle R. NeimanMegan DacekKripa S. GaneshDarren C. JohnsonRamya SridharanKaren L. ChuVinagolu K. RajasekharScott W. Lowe, John D. Chodera, and Daniel A. Heller. 
Nature Materials 17:361, 2018. [DOI] [PDF] [Supporting Info] [nano-drugbank]

In a collaboration with the Heller Lab at MSKCC, we show how indocyanine nanoparticles can package insoluble selective kinase inhibitors with high mass loadings and efficiently deliver them to tumors.