Journal of Computer-Aided Molecular Design

, Volume 18, Issue 10, pp 635–650

Unsupervised guided docking of covalently bound ligands


DOI: 10.1007/s10822-004-5291-4

Cite this article as:
Fradera, X., Kaur, J. & Mestres, J. J Comput Aided Mol Des (2004) 18: 635. doi:10.1007/s10822-004-5291-4


An approach for docking covalently bound ligands in protein enzymes or receptors was implemented in MacDOCK, a similarity-driven docking program based on DOCK 4.0. This approach was tested with a small number of covalent ligand–protein structures, using both native and non-native protein structures. In all cases, MacDOCK was able to generate orientations consistent with the known covalent binding mode of these complexes, with a performance similar to that of other docking programs. This method was also applied to search for known covalent thrombin inhibitors in a medium-sized molecular database (ca. 11,000 compounds). Detection of functional groups suitable for covalent docking was carried out automatically. A significant enrichment in known active molecules in the first 5% of the database was obtained, showing that MacDOCK can be used efficiently for the virtual screening of covalently bound ligands.


covalently bound ligands molecular similarity protein–ligand docking thrombin virtual screening 

Copyright information

© Springer 2005

Authors and Affiliations

  1. 1.Department of Medicinal ChemistryOrganon Laboratories Ltd.Newhouse, LanarkshireScotlandUK
  2. 2.OSI PharmaceuticalsOxfordUK
  3. 3.Institut Municipal d‘Investigació MèdicaUniversitat Pompeu FabraBarcelonaSpain

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