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Journal of Computer-Aided Molecular Design

, Volume 18, Issue 10, pp 635–650 | Cite as

Unsupervised guided docking of covalently bound ligands

  • Xavier FraderaEmail author
  • Jasmit Kaur
  • Jordi Mestres
Article

Summary

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.

Keywords

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

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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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