Volume 3 Supplement 1
Analysis of structure-selectivity relationships through single- or dual step selectivity searching using 2D molecular fingerprints
© Stumpfe et al; licensee BioMed Central Ltd. 2009
Published: 05 June 2009
The identification of small molecules displaying different selectivity patterns against a protein target is a prerequisite to interfere with functions of individual members of protein families . For computational methods it is more difficult to study selectivity than activity because selectivity analysis requires the evaluation of compounds binding to multiple targets .
We aim at the development of computational approaches for the study of structure-selectivity relationships and prediction of target-selective ligands. Therefore, we have designed 18 selectivity sets containing target-selective molecules and compounds that are comparably active against related targets (and thus non-selective). This compound collection of a total of 432 compounds focuses on eight targets belonging to four protein families and has enabled us to evaluate different in silico approaches to search for target-selective compounds .
The results further support previous findings that even low-complexity structure-based 2D fingerprints are capable of identifying compounds having different selectivity against closely related target proteins and revealed a preferred search strategy to enrich database selection sets with target-selective compounds .
- Stockwell BR: Nature. 2004, 432: 846-854. 10.1038/nature03196.View ArticleGoogle Scholar
- Bajorath J: Curr Opin Chem Biol. 2008, 12: 352-358. 10.1016/j.cbpa.2008.01.044.View ArticleGoogle Scholar
- Stumpfe D, Geppert H, Bajorath J: Chem Biol Drug Des. 2008, 71: 518-528. 10.1111/j.1747-0285.2008.00670.x.View ArticleGoogle Scholar
- Stumpfe D, Ahmed HEA, Vogt I, Bajorath J: Chem Biol Drug Des. 2007, 70: 182-194. 10.1111/j.1747-0285.2007.00554.x.View ArticleGoogle Scholar
- Vogt I, Stumpfe D, Ahmed HEA, Bajorath J: Chem Biol Drug Des. 2007, 70: 195-205. 10.1111/j.1747-0285.2007.00555.x.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd.