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Visualisation and subsets of the chemical universe database GDB-13 for virtual screening

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Abstract

The chemical universe database GDB-13, which enumerates 977 million organic molecules up to 13 atoms of C, N, O, S and Cl following simple chemical stability and synthetic feasibility rules, represents a vast reservoir for new fragments. GDB-13 was classified using the MQN-system discussed in the preceding paper for the analysis of PubChem fragments. Two hundred and fifty-five subsets of GDB-13 were generated by the combinatorial use of eight restrictive criteria, including fragment-like (“rule of three”) and scaffold-like (no acyclic carbon atoms) filters. Virtual screening for analogs of 15 commercial drugs of 13 non-hydrogen atoms or less shows that retrieving MQN-neighbors of a query molecule from GDB-13 or its subsets provides on average a 38-fold enrichment in structural analogs (Daylight-type substructure fingerprint Tanimoto T SF > 0.7), and a 75-fold enrichment in shape-similar analogs (ROCS TanimotoCombo score > 1.4). An MQN-searchable version of GDB-13 is provided at www.gdb.unibe.ch.

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Acknowledgments

This work was supported financially by the University of Berne, the Swiss National Science Foundation and the Office Fédéral Suisse de l’Education et de la Science.

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Berne, Freiestrasse 3, 3012, Berne, Switzerland

    Lorenz C. Blum, Ruud van Deursen & Jean-Louis Reymond

  2. Swiss National Center of Competence in Research, NCCR-TransCure, University of Berne, Freiestrasse 3, 3012, Berne, Switzerland

    Lorenz C. Blum, Ruud van Deursen & Jean-Louis Reymond

Authors
  1. Lorenz C. Blum
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  2. Ruud van Deursen
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  3. Jean-Louis Reymond
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Correspondence to Jean-Louis Reymond.

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Blum, L.C., van Deursen, R. & Reymond, JL. Visualisation and subsets of the chemical universe database GDB-13 for virtual screening. J Comput Aided Mol Des 25, 637–647 (2011). https://doi.org/10.1007/s10822-011-9436-y

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  • DOI: https://doi.org/10.1007/s10822-011-9436-y

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