- Poster presentation
- Open Access
Mining public-source databases for structure-activity relationships
© Bernd et al; licensee BioMed Central Ltd. 2010
- Published: 04 May 2010
- Enrichment Analysis
- Structural Detail
- Public Information
- Activity Information
- Reported Activity
Modeling off-target effects has become a highly important and relevant component of the computational chemistry toolset. The presentation will describe a new contribution that seeks to allow the extraction of 3D-structure-activity relationships from public information starting from a chemical structure. Several public source databases such as PubChem  offering structure as well as activity information for a number of targets have been examined for their value in extracting useful structure-activity relationships (SARs). A Topomer search  of public-source databases using the structures of a set of 255 marketed drugs  as queries yielded sets of shape- and pharmacophore similar hits. SAR-tables were constructed by collecting hits around each query structure and for a particular reported activity. A new method: quantitative series enrichment analysis (QSEA)  was applied to these SAR-tables to capture trends and to transform these trends into 3D-QSAR models. Overall more than 400 SAR-tables with Topomer CoMFA models were found by extracting trends from the PubChem and ChemBank  database. The resulting models were able to highlight the structural details of certain off-target effects of marketed drugs even in those cases where the traditional structural similarity would conclude that no off-target effect would exist. This demonstrates the usefulness of the approach in modeling off-target effects.
- Cramer RD: J Chem Inf Comp Sci. 2004, 44: 1221-1227.View ArticleGoogle Scholar
- Cleves AE, Jain AN: J Med Chem. 2006, 49: 2921-2938. 10.1021/jm051139t.View ArticleGoogle Scholar
- Wendt B, Cramer RD: J Comp Aided Mol Des. 2008, 22: 541-555. 10.1007/s10822-008-9195-6.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd.