Journal of Computer-Aided Molecular Design

, Volume 21, Issue 10–11, pp 575–590

Pharmacophore modeling and parallel screening for PPAR ligands

  • Patrick Markt
  • Daniela Schuster
  • Johannes Kirchmair
  • Christian Laggner
  • Thierry Langer
Article

DOI: 10.1007/s10822-007-9140-0

Cite this article as:
Markt, P., Schuster, D., Kirchmair, J. et al. J Comput Aided Mol Des (2007) 21: 575. doi:10.1007/s10822-007-9140-0

Abstract

We describe the generation and validation of pharmacophore models for PPARs, as well as a large scale validation of the parallel screening approach by screening PPAR ligands against a large database of structure-based models. A large test set of 357 PPAR ligands was screened against 48 PPAR models to determine the best models for agonists of PPAR-α, PPAR-δ, and PPAR-γ. Afterwards, a parallel screen was performed using the 357 PPAR ligands and 47 structure-based models for PPARs, which were integrated into a 1537 models comprising in-house pharmacophore database, to assess the enrichment of PPAR ligands within the PPAR hypotheses. For these purposes, we categorized the 1537 database models into 181 protein targets and developed a score that ranks the retrieved targets for each ligand. Thus, we tried to find out if the concept of parallel screening is able to predict the correct pharmacological target for a set of compounds. The PPAR target was ranked first more often than any other target. This confirms the ability of parallel screening to forecast the pharmacological active target for a set of compounds.

Keywords

PPAR LigandScout ilib:diverse Virtual screening Parallel screening Pharmacophore modelling Activity profiling Target fishing 

Supplementary material

10822_2007_9140_MOESM1_ESM.doc (1.1 mb)
(DOC 1111 kb)

Copyright information

© Springer Science+Business Media B.V. 2007

Authors and Affiliations

  • Patrick Markt
    • 1
  • Daniela Schuster
    • 1
    • 2
  • Johannes Kirchmair
    • 1
    • 2
  • Christian Laggner
    • 1
  • Thierry Langer
    • 1
    • 2
  1. 1.Department of Pharmaceutical Chemistry, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck (CMBI)University of InnsbruckInnsbruckAustria
  2. 2.Inte:Ligand Softwareentwicklungs- und Consulting GmbHMaria EnzersdorfAustria

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