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Identification of target-specific bioisosteric fragments from ligand-protein crystallographic data

Kennewell, E., Willett, P., Ducrot, P. and Luttmann, C. (2006) Identification of target-specific bioisosteric fragments from ligand-protein crystallographic data. Journal of Computer-Aided Molecular Design, 20 (6). pp. 385-394. ISSN 0920-654X

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Bioisosteres are functional groups or atoms that are structurally different but that can form similar intermolecular interactions. Potential bioisosteres were identified here from analysing the X-ray crystallographic structures for sets of different ligands complexed with a fixed protein. The protein was used to align the ligands with each other, and then pairs of ligands compared to identify substructural features with high volume overlap that occurred in approximately the same region of geometric space. The resulting pairs of substructural features can suggest potential bioisosteric replacements for use in lead-optimisation studies. Experiments with 12 sets of ligand-protein complexes from the Protein Data Bank demonstrate the effectiveness of the procedure.

Item Type: Article
Copyright, Publisher and Additional Information: © Springer Science+Business Media B.V. 2006. This is an author produced version of a paper published in Journal of Computer-Aided Molecular Design. Uploaded in accordance with the publisher's self-archiving policy.
Keywords: bioisostere, fragment substructure, ligand-protein complex, protein data bank, shape similarity
Institution: The University of Sheffield
Academic Units: The University of Sheffield > Faculty of Social Sciences (Sheffield) > Information School (Sheffield)
The University of Sheffield > University of Sheffield Research Centres and Institutes > The Krebs Institute for Biomolecular Research (Sheffield)
Depositing User: Repository Officer
Date Deposited: 29 Jan 2008 11:24
Last Modified: 08 Feb 2013 16:55
Published Version: http://dx.doi.org/10.1007/s10822-006-9072-0
Status: Published
Publisher: Springer
Refereed: Yes
Identification Number: 10.1007/s10822-006-9072-0
URI: http://eprints.whiterose.ac.uk/id/eprint/3606

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