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Three-Dimensional Protein–Ligand Interaction Scaling of Two-Dimensional Fingerprints

Authors

  • Lu Tan,

    1. Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, D-53113 Bonn, Germany
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  • Martin Vogt,

    1. Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal Chemistry, Rheinische Friedrich-Wilhelms-Universität Bonn, Dahlmannstr. 2, D-53113 Bonn, Germany
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  • Jürgen Bajorath

    Corresponding author
      * Corresponding author: Jürgen Bajorath, bajorath@bit.uni-bonn.de
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* Corresponding author: Jürgen Bajorath, bajorath@bit.uni-bonn.de

Abstract

We introduce a computational scaling methodology that utilizes protein–ligand interaction information extracted from complex crystal structures to enrich similarity searching using structural fingerprints with compound class-specific information. Scaling factors are derived to emphasize fingerprint bit positions that result from interacting fragments of bound ligands and correspond to frequently occurring structural features. Through interaction-based scaling, this information is transferred to standard fingerprints of multiple reference compounds. In systematic search calculations, fingerprints scaled on the basis of three-dimensional information are found to produce higher recall rates of active compounds than alternative types of scaled and non-scaled fingerprints.

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