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Journal of Computer-Aided Molecular Design

, Volume 20, Issue 12, pp 773–788 | Cite as

Efficient overlay of small organic molecules using 3D pharmacophores

  • Gerhard Wolber
  • Alois A. Dornhofer
  • Thierry Langer
Original Paper

Abstract

Aligning and overlaying two or more bio-active molecules is one of the key tasks in computational drug discovery and bio-activity prediction. Especially chemical-functional molecule characteristics from the view point of a macromolecular target represented as a 3D pharmacophore are the most interesting similarity measure when describing and analyzing macromolecule-ligand interaction. In this study, a novel approach for aligning rigid three-dimensional molecules according to their chemical-functional pharmacophoric features is presented and compared to the overlay of experimentally determined poses in a comparable macromolecule coordinate frame. The presented approach identifies optimal chemical feature pairs using distance and density characteristics obtained by correlating pharmacophoric geometries and thus proves to be faster than existing combinatorial alignment methods and creates more reasonable alignments than pure atom-based methods. Examples will be provided to demonstrate the feasibility, speed and intuitiveness of this method.

Keywords

Molecular alignment Molecular superimposition Pharmacophore LigandScout 

Notes

Acknowledgments

We thank Fabian Bendix and Robert Kosara (Inte:Ligand) for their excellent work on LigandScout as well as Christian Laggner, Johannes Kirchmair, Daniela Schuster, Theodora Steindl, and Eva Kleinrath (University of Innsbruck) for testing and helpful discussions.

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Copyright information

© Springer Science+Business Media, LLC 2006

Authors and Affiliations

  • Gerhard Wolber
    • 1
  • Alois A. Dornhofer
    • 1
  • Thierry Langer
    • 2
  1. 1.Inte:Ligand Softwareentwickungs- und Consulting GmbHViennaAustria
  2. 2.Computer-Aided Molecular Design Group, Center of Molecular Biology InnsbruckInstitute of PharmacyInnsbruckAustria

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