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.
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Fradera, X., Kaur, J. & Mestres, J. Unsupervised guided docking of covalently bound ligands. J Comput Aided Mol Des 18, 635–650 (2004). https://doi.org/10.1007/s10822-004-5291-4
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DOI: https://doi.org/10.1007/s10822-004-5291-4