Journal of Computer-Aided Molecular Design

, Volume 22, Issue 8, pp 571–578 | Cite as

Visual exploration of structure–activity relationship using maximum common framework

Article

Abstract

To help tracking all molecules made in a typical medicinal chemistry project, we have developed an algorithm to generate a maximum common framework (MCF) hierarchy and an interactive tool for its visualization and analysis. By identifying all unique frameworks for a set of molecules and all molecules containing each framework, we were able to simplify the MCF hierarchy build up steps and, as a result, speed up the entire process significantly. By allowing compounds to be assigned to multiple MCFs, users can easily remove bad branching nodes and concentrate on interesting ones. MCF hierarchies provide an effective and intuitive visualization for tracking medicinal chemistry lead optimization projects. We will provide examples to illustrate its usefulness.

Keywords

Visual exploration Structure–activity relationship Maximum common framework 

References

  1. 1.
    Pargellis C, Tong L, Churchill L, Cirillo PF, Gilmore T, Graham AG, Grob PM, Hickey ER, Moss N, Pav S, Regan J (2002) Nature Struct Biol 9:268–272CrossRefGoogle Scholar
  2. 2.
    Bemis GW, Murcko MA (1996) J Med Chem 39:2887–2893CrossRefGoogle Scholar
  3. 3.
    Wilkens SJ, Janes J, Su AI, Hier S (2005) J Med Chem 48:3182–3193CrossRefGoogle Scholar
  4. 4.
    Schuffenhauer A, Ertl P, Roggo S, Wetzel S, Marcus AK, Waldmann H (2007) J Chem Inf Model 47:47–58CrossRefGoogle Scholar
  5. 5.
    Schuffenhauer A, Brown N, Ertl P, Jenkins JL, Selzer P, Hamon J (2007) J Chem Inf Model 47:325–336CrossRefGoogle Scholar
  6. 6.
    Koch MA, Schuffenhauer A, Scheck M, Wetzel S, Casaulta M, Odermatt A, Ertl P, Waldmann H (2005) PNAS 102:17272–17277CrossRefGoogle Scholar
  7. 7.
    The OEChem toolkit is available from OpenEye Scientific Software, Inc. http://www.eyesopen.com
  8. 8.
    The Qt class library and tools are available from Trolltech Inc. http://www.trolltech.com
  9. 9.
    Cho SJ, Sun Y, Harte W (2006) J Comput-Aided Mol Des 20:249–261CrossRefGoogle Scholar
  10. 10.
    Target Inhibitor Databases are available from GVK Biosciences Private Limited. http://www.gvkbio.com
  11. 11.
    Molecular Design Drug Data Report, version 2005.2. Molecular Design Ltd., San Leandro, CAGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  1. 1.Molecular StructureAmgenThousand OaksUSA
  2. 2.CHDI, Inc.Los AngelesUSA

Personalised recommendations