Skip to main content

Mining public-source databases for structure-activity relationships

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 [1] 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 [2] of public-source databases using the structures of a set of 255 marketed drugs [3] 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) [4] 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 [5] 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.

References

  1. 1.

    [http://pubchem.ncbi.nlm.nih.gov]

  2. 2.

    Cramer RD: J Chem Inf Comp Sci. 2004, 44: 1221-1227.

    Article  Google Scholar 

  3. 3.

    Cleves AE, Jain AN: J Med Chem. 2006, 49: 2921-2938. 10.1021/jm051139t.

    CAS  Article  Google Scholar 

  4. 4.

    Wendt B, Cramer RD: J Comp Aided Mol Des. 2008, 22: 541-555. 10.1007/s10822-008-9195-6.

    CAS  Article  Google Scholar 

  5. 5.

    [http://chembank.broad.harvard.edu/]

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Bernd Wendt.

Rights and permissions

Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License ( https://creativecommons.org/licenses/by-nc/2.0 ), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Reprints and Permissions

About this article

Cite this article

Wendt, B., Bös, F. & Uhrig, U. Mining public-source databases for structure-activity relationships. J Cheminform 2, P4 (2010). https://doi.org/10.1186/1758-2946-2-S1-P4

Download citation

Keywords

  • Enrichment Analysis
  • Structural Detail
  • Public Information
  • Activity Information
  • Reported Activity