Jul 10, 2016

Measuring experimental cyclohexane-water distribution coefficients for the SAMPL5 challenge

BioRxiv : the Preprint Server for Biology
Ariën S RustenburgJohn D. Chodera

Abstract

Small molecule distribution coefficients between immiscible nonaqueuous and aqueous phases\---|such as cyclohexane and water\---| the degree to which small molecules prefer one phase over another at a given pH. As distribution coefficients capture both thermodynamic effects (the free energy of transfer between phases) and chemical effects (protonation state and tautomer effects in aqueous solution), they provide an exacting test of the thermodynamic and chemical accuracy of physical models without the long correlation times inherent to the prediction of more complex properties of relevance to drug discovery, such as protein-ligand binding affinities. For the SAMPL5 challenge, we carried out a blind prediction exercise in which participants were tasked with the prediction of distribution coefficients to assess its potential as a new route for the evaluation and systematic improvement of predictive physical models. These measurements are typically performed for octanol-water, but we opted to utilize cyclohexane for the nonpolar phase. Cyclohexane was suggested to avoid issues with the high water content and persistent heterogeneous structure of water- saturated octanol phases, since it has which has greatly reduced water content ...Continue Reading

  • References
  • Citations

References

  • We're still populating references for this paper, please check back later.
  • References
  • Citations

Citations

  • This paper may not have been cited yet.

Mentioned in this Paper

Research
Tautomer
Ligand Binding
Tandem Mass Spectrometry
Evaluation
Participant
Pharmacologic Substance
Binding (Molecular Function)
Cyclohexanal
Structure

About this Paper

Related Feeds

BioRxiv & MedRxiv Preprints

BioRxiv and MedRxiv are the preprint servers for biology and health sciences respectively, operated by Cold Spring Harbor Laboratory. Here are the latest preprint articles (which are not peer-reviewed) from BioRxiv and MedRxiv.

Related Papers

Journal of Computer-aided Molecular Design
Ariën S RustenburgJohn D. Chodera
Journal of Computer-aided Molecular Design
Caitlin C BannanDavid L. Mobley
European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Axel AndrésJosep M Huerta
© 2020 Meta ULC. All rights reserved