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Journal of Computer-Aided Molecular Design

, Volume 22, Issue 2, pp 111–118 | Cite as

FTree query construction for virtual screening: a statistical analysis

  • Christof Gerlach
  • Howard Broughton
  • Andrea ZalianiEmail author
Article

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.

Keywords

Feature trees MDDR ZINC Query building Database profiling FTrees 

Notes

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.

Supplementary material

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Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Christof Gerlach
    • 1
    • 2
  • Howard Broughton
    • 3
  • Andrea Zaliani
    • 1
    • 4
    Email author
  1. 1.Eli Lilly & Co. Research LaboratoriesHamburgGermany
  2. 2.Bayer-Schering Pharma AGBerlinGermany
  3. 3.Discovery Chemistry Research and Technologies, Lilly Research Laboratories, Centro de Investigacion LillyAlcobendas, MadridSpain
  4. 4.Zentrum für BioinformatikUniversität HamburgHamburgGermany

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