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Efficient overlay of small organic molecules using 3D pharmacophores

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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.

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References

  1. Krovat EM, Fruhwirth KH, Langer T (2005) J Chem Inf Model 1:146

    Google Scholar 

  2. Laggner C, Schieferer C, Fiechtner B, Poles G, Hoffmann RD, Glossmann H, Langer T, Moebius FF (2005) J Med Chem 15:4754

    Article  Google Scholar 

  3. Schuster D, Laggner C, Steindl TM, Palusczak A, Hartmann RW, Langer T (2006) J Chem Inf Model 3:1301

    Google Scholar 

  4. Schuster D, Laggner C, Steindl TM, Langer T (2006) Curr Drug Discov Technol 1:1

    Article  Google Scholar 

  5. Steindl T, Laggner C, Langer T (2005) J Chem Inf Model 3:716

    Article  Google Scholar 

  6. Böhm H-J, Klebe G, Kubinyi H (1996) Spektrum Akademischer Verlag

  7. Lemmen C, Lengauer T (2000) J Comput Aided Mol Des 3:215

    Article  Google Scholar 

  8. Martin YC, Bures MG, Danaher EA, DeLazzer J, Lico I, Pavlik PA (1993) J Comput Aided Mol Des 1:83

    Article  Google Scholar 

  9. Bron C, Kerbosch J (1973) Commun ACM 9:575

    Article  Google Scholar 

  10. Barnum D, Greene J, Smellie A, Sprague P (1996) J Chem Inf Comput Sci 3:563

    Article  Google Scholar 

  11. Langer T, Krovat EM (2003) Curr Opin Drug Discov Devel 3:370

    Google Scholar 

  12. Langer T, Hoffmann RD (2001) Curr Pharm Des 7:509

    Article  CAS  Google Scholar 

  13. DS Visualizer, version 1.5, available from Accelrys, Inc., 10188 Telesis Court, Suite 100, San Diego, CA 92121, USA

  14. Jones G, Willett P, Glen RC (1995) J Comput Aided Mol Des 6:532

    Article  Google Scholar 

  15. Prabhu NV, Zhu P, Sharp KA (2004) J Comp Chem 16:2049

    Article  Google Scholar 

  16. EON, available from OpenEye Scientific Software (www.eyesopen.com), 3600 Cerrillos Rd., Suite 1107, Santa Fe, NM 87507, USA

  17. Haigh JA, Pickup BT, Grant JA, Nicholls A (2005) J Chem Inf Model 3:673

    Article  Google Scholar 

  18. ROCS, available from OpenEye Scientific Software (www.eyesopen.com), 3600 Cerrillos Rd., Suite 1107, Santa Fe, NM 87507, USA

  19. Bostrom J (2001) J Comput Aided Mol Des 12:1137

    Article  Google Scholar 

  20. Kirchmair J, Laggner C, Wolber G, Langer T (2005) J Chem Inf Model 2:422

    Article  Google Scholar 

  21. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) Nucleic Acids Res 1:235

    Article  Google Scholar 

  22. Kirchmair J, Wolber G, Laggner C, Langer T (2006) J Chem Inf Model 46:1848

    Article  CAS  Google Scholar 

  23. Bostrom J, Greenwood JR, Gottfries J (2003) J Mol Graph Model 5:449

    Article  Google Scholar 

  24. Richmond NJ, Willett P, Clark RD (2004) J Mol Graph Model 2:199

    Article  Google Scholar 

  25. Kuhn HW (1955) Naval Res Logist Quart 2:83

    Google Scholar 

  26. Wolber G, Langer T (2005) J Chem Inf Model 1:160

    Google Scholar 

  27. Kabsch W (1976) Acta Crystal 922

  28. Kabsch W (1978) Acta Crystal 827

  29. Wolber G, Langer T (2001) In: Rational approaches to drug design, H.-D.H.W. Sippl, Editor. 2001, Prous Science: Barcelona, pp. 390–399

  30. OMEGA, version 2.0, available from OpenEye Scientific Software (www.eyesopen.com), 3600 Cerrillos Rd., Suite 1107, Santa Fe, NM 87507, USA

  31. Cramer RD 3rd, Patterson DE, Bunce JD (1989) Prog Clin Biol Res 161

  32. Kubinyi HF, G, Martin YC (1998) Vol. 1–3, Kluwer/ESCOM, Dordrecht

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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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Authors and Affiliations

  1. Inte:Ligand Softwareentwickungs- und Consulting GmbH, Mariahilferstrasse 74B/11, Vienna, 1070, Austria

    Gerhard Wolber & Alois A. Dornhofer

  2. Computer-Aided Molecular Design Group, Center of Molecular Biology Innsbruck, Institute of Pharmacy, Innrain 52a, Innsbruck, 6020, Austria

    Thierry Langer

Authors
  1. Gerhard Wolber
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  2. Alois A. Dornhofer
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  3. Thierry Langer
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Correspondence to Gerhard Wolber.

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Wolber, G., Dornhofer, A.A. & Langer, T. Efficient overlay of small organic molecules using 3D pharmacophores. J Comput Aided Mol Des 20, 773–788 (2006). https://doi.org/10.1007/s10822-006-9078-7

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  • DOI: https://doi.org/10.1007/s10822-006-9078-7

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