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FTree query construction for virtual screening: a statistical analysis

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Abstract

FTrees (FT) is a known chemoinformatic tool able to condense molecular descriptions into a graph object and to search for actives in large databases using graph similarity. The query graph is classically derived from a known active molecule, or a set of actives, for which a similar compound has to be found. Recently, FT similarity has been extended to fragment space, widening its capabilities. If a user were able to build a knowledge-based FT query from information other than a known active structure, the similarity search could be combined with other, normally separate, fields like de-novo design or pharmacophore searches. With this aim in mind, we performed a comprehensive analysis of several databases in terms of FT description and provide a basic statistical analysis of the FT spaces so far at hand. Vendors’ catalogue collections and MDDR as a source of potential or known “actives”, respectively, have been used. With the results reported herein, a set of ranges, mean values and standard deviations for several query parameters are presented in order to set a reference guide for the users. Applications on how to use this information in FT query building are also provided, using a newly built 3D-pharmacophore from 57 5HT-1F agonists and a published one which was used for virtual screening for tRNA-guanine transglycosylase (TGT) inhibitors.

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Acknowledgements

We are in debt to Joerg Degen and Prof. Matthias Rarey (ZBH, Hamburg) for their suggestions and to the reviewers for their constructing criticism.

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Author notes

  1. Christof Gerlach

    Present address: Bayer-Schering Pharma AG, Müllerstrasse 178, 13342, Berlin, Germany

Authors and Affiliations

  1. Eli Lilly & Co. Research Laboratories, Essener Bogen 7, 22419, Hamburg, Germany

    Christof Gerlach & Andrea Zaliani

  2. Discovery Chemistry Research and Technologies, Lilly Research Laboratories, Centro de Investigacion Lilly, Avenida de la Industria 30, 28108, Alcobendas, Madrid, Spain

    Howard Broughton

  3. Zentrum für Bioinformatik, Universität Hamburg, Bundesstrasse 43, 20146, Hamburg, Germany

    Andrea Zaliani

Authors
  1. Christof Gerlach
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  2. Howard Broughton
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Corresponding author

Correspondence to Andrea Zaliani.

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Gerlach, C., Broughton, H. & Zaliani, A. FTree query construction for virtual screening: a statistical analysis. J Comput Aided Mol Des 22, 111–118 (2008). https://doi.org/10.1007/s10822-008-9178-7

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  • DOI: https://doi.org/10.1007/s10822-008-9178-7

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