PhAST: pharmacophore alignment search tool

Journal of Computational Chemistry
Volker HähnkeGisbert Schneider

Abstract

We present a ligand-based virtual screening technique (PhAST) for rapid hit and lead structure searching in large compound databases. Molecules are represented as strings encoding the distribution of pharmacophoric features on the molecular graph. In contrast to other text-based methods using SMILES strings, we introduce a new form of text representation that describes the pharmacophore of molecules. This string representation opens the opportunity for revealing functional similarity between molecules by sequence alignment techniques in analogy to homology searching in protein or nucleic acid sequence databases. We favorably compared PhAST with other current ligand-based virtual screening methods in a retrospective analysis using the BEDROC metric. In a prospective application, PhAST identified two novel inhibitors of 5-lipoxygenase product formation with minimal experimental effort. This outcome demonstrates the applicability of PhAST to drug discovery projects and provides an innovative concept of sequence-based compound screening with substantial scaffold hopping potential.

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Citations

Aug 9, 2011·Journal of Chemical Information and Modeling·Matthew A KayalaPierre Baldi
Sep 18, 2012·Journal of Chemical Information and Modeling·Matthew A Kayala, Pierre Baldi
Apr 2, 2011·Future Medicinal Chemistry·Michael C Hutter
Dec 19, 2014·BMC Bioinformatics·Lingxiao ZhouBruno Gaeta
Sep 15, 2010·Journal of Computational Chemistry·Volker HähnkeGisbert Schneider
Jul 1, 2013·Molecular Informatics·Volker HähnkeGisbert Schneider
Feb 18, 2011·Journal of Computational Chemistry·Volker HähnkeGisbert Schneider
Feb 18, 2011·Journal of Computational Chemistry·Volker Hähnke, Gisbert Schneider
Oct 5, 2018·BMC Bioinformatics·Patrick Kunzmann, Kay Hamacher
Aug 21, 2013·Basic & Clinical Pharmacology & Toxicology·Dieter Steinhilber, Bettina Hofmann
May 1, 2009·Journal of Chemical Information and Modeling·Markus Krier, Michael C Hutter
Feb 27, 2019·Journal of Chemical Information and Modeling·Tobias Fehlmann, Michael C Hutter

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