Parallel Screening:  A Novel Concept in Pharmacophore Modeling and Virtual Screening†

Theodora M. Steindl,‡§ Daniela Schuster,‡ Christian Laggner,‡ and Thierry Langer*‡§
Institute of Pharmacy, Computer Aided Molecular Design Group, University of Innsbruck, Innrain 52c, Austria, Center for Molecular Biosciences Innsbruck (CMBI), Peter-Mair-Str.1, A-6020 Innsbruck, Austria, and Inte:Ligand GmbH, Clemens Maria Hofbauer-Gasse 6, A-2344 Maria Enzersdorf, Austria
J. Chem. Inf. Model., 2006, 46 (5), pp 2146–2157
DOI: 10.1021/ci6002043
Publication Date (Web): August 23, 2006
Copyright © 2006 American Chemical Society
†

 Parts of this study have been presented at the 9th E.U. Catalyst User Group Meeting 2006, March 23, 2006, Frankfurt, Germany, and at the 231st ACS National Meeting, March 29, 2006, Atlanta, GA, as an oral presentation.

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‡

 University of Innsbruck and CMBI.

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§

 Inte:Ligand GmbH.

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*

 To whom correspondence should be addressed. Tel.:  +43 512 507 5252. Fax +43 512 507 5269. E-mail:  thierry.langer@uibk.ac.at.

Abstract

Parallel screening comprises a novel in silico method to predict the potential biological activities of a compound by screening it with a multitude of pharmacophore models. Our aim is to provide a fast, large-scale system that allows for virtual activity profiling. In this proof of principle study, carried out with the software tools LigandScout and Catalyst, we present a model work for the application of parallel pharmacophore-based virtual screening on a set of 50 structure-based pharmacophore models built for various viral targets and 100 antiviral compounds. The latter were screened against all pharmacophore models in order to determine if their biological targets could be correctly predicted via an enrichment of corresponding pharmacophores matching these ligands. The results demonstrate that the desired enrichment, that is, successful virtual activity profiling, was achieved for approximately 90% of all input molecules. We discuss descriptors for output validation, as well as various aspects influencing the analysis of the obtained activity profiles, and the effect of the utilized search modus for screening.

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  • Published In Issue September 25, 2006
  • Received May 18, 2006

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