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Pharmacophore alignment search tool: Influence of canonical atom labeling on similarity searching
Article first published online: 1 JUN 2010
DOI: 10.1002/jcc.21574
Copyright © 2010 Wiley Periodicals, Inc.
Additional Information
How to Cite
Hähnke, V., Rupp, M., Krier, M., Rippmann, F. and Schneider, G. (2010), Pharmacophore alignment search tool: Influence of canonical atom labeling on similarity searching. Journal of Computational Chemistry, 31: 2810–2826. doi: 10.1002/jcc.21574
Publication History
- Issue published online: 8 SEP 2010
- Article first published online: 1 JUN 2010
- Manuscript Accepted: 7 APR 2010
- Manuscript Revised: 7 APR 2010
- Manuscript Received: 10 FEB 2010
Keywords:
- global alignment;
- line notation;
- molecular graph;
- similarity;
- virtual screening
Graphical Abstract
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. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010