Skip to main content

Analysis of structure-selectivity relationships through single- or dual step selectivity searching using 2D molecular fingerprints

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 [1]. For computational methods it is more difficult to study selectivity than activity because selectivity analysis requires the evaluation of compounds binding to multiple targets [2].

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 [3].

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 [4][5].


  1. 1.

    Stockwell BR: Nature. 2004, 432: 846-854. 10.1038/nature03196.

    CAS  Article  Google Scholar 

  2. 2.

    Bajorath J: Curr Opin Chem Biol. 2008, 12: 352-358. 10.1016/j.cbpa.2008.01.044.

    CAS  Article  Google Scholar 

  3. 3.

    Stumpfe D, Geppert H, Bajorath J: Chem Biol Drug Des. 2008, 71: 518-528. 10.1111/j.1747-0285.2008.00670.x.

    CAS  Article  Google Scholar 

  4. 4.

    Stumpfe D, Ahmed HEA, Vogt I, Bajorath J: Chem Biol Drug Des. 2007, 70: 182-194. 10.1111/j.1747-0285.2007.00554.x.

    CAS  Article  Google Scholar 

  5. 5.

    Vogt I, Stumpfe D, Ahmed HEA, Bajorath J: Chem Biol Drug Des. 2007, 70: 195-205. 10.1111/j.1747-0285.2007.00555.x.

    CAS  Article  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to J Bajorath.

Rights and permissions

Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License ( ), 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

Stumpfe, D., Geppert, H. & Bajorath, J. Analysis of structure-selectivity relationships through single- or dual step selectivity searching using 2D molecular fingerprints. Chemistry Central Journal 3, P4 (2009).

Download citation


  • Protein Family
  • Computational Approach
  • Individual Member
  • Multiple Target
  • Related Target