title: Pharmacophore alignment search tool: Influence of canonical atom labeling on similarity searching.
abstract: Previously, (Hähnke et al., J Comput Chem 2009, 30, 761) we presented the Pharmacophore Alignment Search Tool (PhAST), a ligand-based virtual screening technique representing molecules as strings coding pharmacophoric features and comparing them by global pairwise sequence alignment. To guarantee unambiguity during the reduction of two-dimensional molecular graphs to one-dimensional strings, PhAST employs a graph canonization step. Here, we present the results of the comparison of 11 different algorithms for graph canonization with respect to their impact on virtual screening. Retrospective screenings of a drug-like data set were evaluated using the BEDROC metric, which yielded averaged values between 0.4 and 0.14 for the best-performing and worst-performing canonization technique. We compared five scoring schemes for the alignments and found preferred combinations of canonization algorithms and scoring functions. Finally, we introduce a performance index that helps prioritize canonization approaches without the need for extensive retrospective evaluation.
authors.affiliation: Johann Wolfgang-Goethe University, Frankfurt am Main 60323, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Hähnke
authors.forename: Matthias
authors.initials: M
authors.lastname: Rupp
authors.forename: Mireille
authors.initials: M
authors.lastname: Krier
authors.forename: Friedrich
authors.initials: F
authors.lastname: Rippmann
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000465:Algorithms; D019295:Computational Biology / Q000379:methods*; D016208:Databases, Factual; D055808:Drug Discovery / Q000379:methods*; D025341:Principal Component Analysis; D016415:Sequence Alignment / Q000379:methods*; D054852:Small Molecule Libraries
chemical_list: D054852:Small Molecule Libraries