Brief Communication | Published:

Interactive exploration of chemical space with Scaffold Hunter

Nature Chemical Biology volume 5, pages 581583 (2009) | Download Citation

  • A Corrigendum to this article was published on 01 September 2009

This article has been updated

Abstract

We describe Scaffold Hunter, a highly interactive computer-based tool for navigation in chemical space that fosters intuitive recognition of complex structural relationships associated with bioactivity. The program reads compound structures and bioactivity data, generates compound scaffolds, correlates them in a hierarchical tree-like arrangement, and annotates them with bioactivity. Brachiation along tree branches from structurally complex to simple scaffolds allows identification of new ligand types. We provide proof of concept for pyruvate kinase.

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Change history

  • 18 August 2009

    In the version of this article initially published, reference 10 was incorrect. The correct reference is: Olah, M. et al. in Chemical Biology: from Small Molecules to Systems Biology and Drug Design (eds. Schreiber, S.L., Kapoor, T.M. & Wess, G.) 760–786 (Wiley-VCH, Weinheim, Germany, 2007). The error has been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank the members of the project group PG504—namely A.B. Ahmed, A. Arndt, P. Büdenbender, V. Bembenek, A. Gorecki, N. Kriege, S. Rakov, M. Rex, G. Schrader, H. Wagner, A. Wiesniewski and C. Yücel—for their enthusiasm and commitment. This work was supported by the Max Planck Society, the State of North-Rhine Westphalia, the European Union Fonds for Regional Development, and the German Federal Ministry for Education and Research through the German National Genome Research Network-Plus (NGFN-Plus, grant number BMBF 01GS08102 to D.R. and H.W.). Part of this work was supported by US National Institutes of Health grant 1U54MH084690 (to T.I.O.). Software was generously supplied by Openeye (OEChem) and Accelrys/SciTegic (PipelinePilot). S.W. is grateful to Novartis for a PhD scholarship.

Author information

Author notes

    • Steffen Renner

    Present address: Novartis Institutes for BioMedical Research, Basel, Switzerland.

Affiliations

  1. Chemical Biology, Max-Planck-Institute of Molecular Physiology, Dortmund, Germany.

    • Stefan Wetzel
    • , Steffen Renner
    •  & Herbert Waldmann
  2. Chemical Biology, Technical University of Dortmund, Dortmund, Germany.

    • Stefan Wetzel
    • , Steffen Renner
    •  & Herbert Waldmann
  3. Chair of Algorithm Engineering, Department of Computer Science, Technical University Dortmund, Dortmund, Germany.

    • Karsten Klein
    •  & Petra Mutzel
  4. Chemical Genomics Centre of the Max Planck Society, Dortmund, Germany.

    • Daniel Rauh
  5. University of New Mexico School of Medicine, Division of Biocomputing, University of New Mexico, Albuquerque, New Mexico, USA.

    • Tudor I Oprea

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Competing interests

T.I.O. is the founder and CEO of Sunset Molecular Discovery LLC, and cofounder of Drug4Cast LLC; both companies provide services related to the pharmaceutical sector. T.I.O. also serves on the scientific advisory board for ChemDiv, Inc.

Corresponding author

Correspondence to Herbert Waldmann.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figure 1, Supplementary Tables 1–9 and Supplementary Methods

Videos

  1. 1.

    Supplementary Movie 1

    Scaffold Hunter – A Guided Tour

  2. 2.

    Supplementary Movie 2

    Exploring Virtual Scaffolds

Zip files

  1. 1.

    Supplementary Software 1

    ZIP archive containing Scaffold Hunter and Scaffold Tree Generator program files

About this article

Publication history

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DOI

https://doi.org/10.1038/nchembio.187

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