Prediction of the permeability of neutral drugs inferred from their solvation properties

Bioinformatics. 2016 Apr 15;32(8):1163-9. doi: 10.1093/bioinformatics/btv725. Epub 2015 Dec 10.

Abstract

Motivation: Determination of drug absorption is an important component of the drug discovery and development process in that it plays a key role in the decision to promote drug candidates to clinical trials. We have developed a method that, on the basis of an analysis of the dynamic distribution of water molecules around a compound obtained by molecular dynamics simulations, can compute a parameter-free value that correlates very well with the compound permeability measured using the human colon adenocarcinoma (Caco-2) cell line assay.

Results: The method has been tested on twenty-three neutral drugs for which a consistent set of experimental data is available. We show here that our method reproduces the experimental data better than other existing tools. Furthermore it provides a detailed view of the relationship between the hydration and the permeability properties of molecules.

Contact: anna.tramontano@uniroma1.it

Supplementary information: Supplementary data are available at Bioinformatics online.

MeSH terms

  • Algorithms*
  • Caco-2 Cells
  • Drug Discovery*
  • Humans
  • Permeability
  • Structure-Activity Relationship
  • Water

Substances

  • Water