Enrichment of True Positives from Structural Alerts Through the Use of Novel Atomic Fragment Based Descriptors

Authors

  • Anthony Long,

    1. Lhasa Ltd. 22-23 Blenheim Terrace, Woodhouse Lane, Leeds, LS2 9HD, UK
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  • Patrik Rydberg

    Corresponding author
    1. Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen phone/fax: (+45) 35 33 66 50/(+45) 35 33 60 41
    • Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen phone/fax: (+45) 35 33 66 50/(+45) 35 33 60 41
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Abstract

To enhance the discrimination rate for methods applying structural alerts and biotransformation rules in the prediction of toxicity and drug metabolism we have developed a set of novel fragment based atomic descriptors. These atomic descriptors encode the properties of the fragments separating an atom from the closest end of a branch or the molecule. The end of a branch and the end of a molecule, as well as the selection of the fragments, are made by an algorithm that uses only the distance matrix of the molecule. The novel descriptors are applied to a small set of biotransformation rules and are shown to be able to reduce the number of unconfirmed positives by up to 58 %.

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