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Journal of Computer-Aided Molecular Design

, Volume 30, Issue 6, pp 447–456 | Cite as

Binding mode similarity measures for ranking of docking poses: a case study on the adenosine A2A receptor

  • Andrew Anighoro
  • Jürgen BajorathEmail author
Article

Abstract

We report an investigation designed to explore alternative approaches for ranking of docking poses in the search for antagonists of the adenosine A2A receptor, an attractive target for structure-based virtual screening. Calculation of 3D similarity of docking poses to crystallographic ligand(s) as well as similarity of receptor–ligand interaction patterns was consistently superior to conventional scoring functions for prioritizing antagonists over decoys. Moreover, the use of crystallographic antagonists and agonists, a core fragment of an antagonist, and a model of an agonist placed into the binding site of an antagonist-bound form of the receptor resulted in a significant early enrichment of antagonists in compound rankings. Taken together, these findings showed that the use of binding modes of agonists and/or antagonists, even if they were only approximate, for similarity assessment of docking poses or comparison of interaction patterns increased the odds of identifying new active compounds over conventional scoring.

Keywords

Molecular docking Virtual screening Binding modes Compound ranking 3D similarity Protein–ligand interaction fingerprints 

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Life Science Informatics, B-IT, LIMES Program Unit Chemical Biology and Medicinal ChemistryRheinische Friedrich-Wilhelms-UniversitätBonnGermany

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