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PhAST: Pharmacophore alignment search tool
Author(s) -
Hähnke Volker,
Hofmann Bettina,
Grgat Tomislav,
Proschak Ewgenij,
Steinhilber Dieter,
Schneider Gisbert
Publication year - 2008
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.21095
Subject(s) - pharmacophore , computer science , virtual screening , nearest neighbor search , computational biology , metric (unit) , chemistry , data mining , stereochemistry , biology , engineering , operations management
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. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2009