Journal of Computer-Aided Molecular Design

, Volume 26, Issue 7, pp 805–819 | Cite as

R-group template CoMFA combines benefits of “ad hoc” and topomer alignments using 3D-QSAR for lead optimization

  • Richard D. Cramer


Template CoMFA methodologies extend topomer CoMFA by allowing user-designated templates, for example the experimental receptor-bound conformation of a prototypical ligand, to help determine the alignment of training and test set structures for 3D-QSAR. The algorithms that generate its new structural modality, template-constrained topomers, are described. Template CoMFA’s resolution of certain topomer CoMFA concerns, by providing user control of topological consistency and structural acceptability, is demonstrated for sixteen 3D-QSAR training sets, in particular the Selwood dataset.


3D-QSAR Topomers Selwood Template CoMFA Ligand alignment 



It is a great pleasure to thank Bernd Wendt for calling attention to the didactic features of the Selwood data set.

Supplementary material

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  1. 1.
    Paul SM, Mytelka DS, Dunwiddie CT, Persinger CC, Munos BH, Lindberg SR, Schacht AL (2010) Nat Rev Drug Disc 9:203–214Google Scholar
  2. 2.
    Cramer RD, Cruz P, Stahl G, Curtiss WC, Campbell B, Masek BB, Soltanshahi F (2008) J Chem Inf Model 48:2180–2195CrossRefGoogle Scholar
  3. 3.
    Doweyko A (2007) J Comp Aided Drug Des 18:587–596CrossRefGoogle Scholar
  4. 4.
    Stouch TR (2012) J Comp Aided Drug Des 26:125–134CrossRefGoogle Scholar
  5. 5.
    Cramer RD, Clark RD, Patterson DE, Ferguson AM (1996) J Med Chem 39:3060–3069CrossRefGoogle Scholar
  6. 6.
    Jilek RJ, Cramer RD (2004) J Chem Inf Comp Sci 44:1221–1227CrossRefGoogle Scholar
  7. 7.
    Cramer RD, Jilek RJ, Guessregen S, Clark SJ, Wendt B, Clark RD (2004) J Med Chem 47(6777):6791Google Scholar
  8. 8.
    Cramer RD (2003) J Med Chem 46:374–389CrossRefGoogle Scholar
  9. 9.
    Cramer RD (2012) J Comp Aided Drug Des 25:197–201CrossRefGoogle Scholar
  10. 10.
    Selwood DL, Livingston DJ, Comley JCW, O’Dowd AB, Hudson AT, Jackson P, Jandu KS, Rose VS, Stables JM (1990) J Med Chem 33:136–142CrossRefGoogle Scholar
  11. 11.
    Nicoletti O, Gillet VJ, Fleming PJ, Green DVS (2002) J Med Chem 45:5069–5080CrossRefGoogle Scholar
  12. 12.
    Kubinyi H (1994) Quant Struct Act Relat 13:285–294Google Scholar
  13. 13.
    So S-S, Karplus M (1996) J Med Chem 39:1521–1540CrossRefGoogle Scholar
  14. 14.
    Wendt B, Cramer RD (2008) J Comp Aided Drug Des 22:541–551CrossRefGoogle Scholar
  15. 15.
    Jain AN (2004) J Med Chem 47:941–961Google Scholar
  16. 16.
    Maggiora GM (2006) J Chem Inf Model 46:1535CrossRefGoogle Scholar
  17. 17.
    Taleb NN (2007) The Black Swan: the impact of the highly Improbable, Random House, ISBN 978-1-4000-6351-2Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Tripos DESt. LouisUSA

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