CONFIRM: connecting fragments found in receptor molecules

  • David C. Thompson
  • R. Aldrin Denny
  • Ramaswamy Nilakantan
  • Christine Humblet
  • Diane Joseph-McCarthy
  • Eric Feyfant
Article

DOI: 10.1007/s10822-008-9221-8

Cite this article as:
Thompson, D.C., Aldrin Denny, R., Nilakantan, R. et al. J Comput Aided Mol Des (2008) 22: 761. doi:10.1007/s10822-008-9221-8

Abstract

A novel algorithm for the connecting of fragment molecules is presented and validated for a number of test systems. Within the CONFIRM (Connecting Fragments Found in Receptor Molecules) approach a pre-prepared library of bridges is searched to extract those which match a search criterion derived from known experimental or computational binding information about fragment molecules within a target binding site. The resulting bridge ‘hits’ are then connected, in an automated fashion, to the fragments and docked into the target receptor. Docking poses are assessed in terms of root-mean-squared deviation from the known positions of the fragment molecules, as well as docking score should known inhibitors be available. The creation of the bridge library, the full details and novelty of the CONFIRM algorithm, and the general applicability of this approach within the field of fragment-based de novo drug design are discussed.

Keywords

Bridge library Connecting fragments Fragment-based de novo design Molecular docking Structure-based drug design 

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • David C. Thompson
    • 1
  • R. Aldrin Denny
    • 1
  • Ramaswamy Nilakantan
    • 1
  • Christine Humblet
    • 2
  • Diane Joseph-McCarthy
    • 1
  • Eric Feyfant
    • 1
  1. 1.Wyeth Research, Chemical and Screening SciencesCambridgeUSA
  2. 2.Wyeth Research, Chemical and Screening SciencesPrincetonUSA

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