Cottrell, S.J., Gillet, V.J., Taylor, R. et al. (1 more author) (2004) Generation of multiple pharmacophore hypotheses using multiobjective optimisation techniques. Journal of Computer-Aided Molecular Design, 18 (11). 665 - 682.
Abstract
Pharmacophore methods provide a way of establishing a structure--activity relationship for a series of known active ligands. Often, there are several plausible hypotheses that could explain the same set of ligands and, in such cases, it is important that the chemist is presented with alternatives that can be tested with different synthetic compounds. Existing pharmacophore methods involve either generating an ensemble of conformers and considering each conformer of each ligand in turn or exploring conformational space on-the-fly. The ensemble methods tend to produce a large number of hypotheses and require considerable effort to analyse the results, whereas methods that vary conformation on-the-fly typically generate a single solution that represents one possible hypothesis, even though several might exist. We describe a new method for generating multiple pharmacophore hypotheses with full conformational flexibility being explored on-the-fly. The method is based on multiobjective evolutionary algorithm techniques and is designed to search for an ensemble of diverse yet plausible overlays which can then be presented to the chemist for further investigation.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2004 Kluwer Academic Publishers. This is an author produced version of a paper subsequently published in Journal of Computer-Aided Molecular Design. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Pharmacophore identification; Molecular overlay; Alignment; Evolutionary algorithms; MOGA; Multiobjective optimisation; Multiobjective genetic algorithm; Conformational analysis. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Social Sciences (Sheffield) > Department of Geography (Sheffield) The University of Sheffield > Faculty of Social Sciences (Sheffield) > Information School (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 23 Apr 2014 08:49 |
Last Modified: | 23 Apr 2014 08:49 |
Published Version: | http://dx.doi.org/10.1007/s10822-004-5523-7 |
Status: | Published |
Publisher: | Kluwer Academic Publishers |
Refereed: | Yes |
Identification Number: | 10.1007/s10822-004-5523-7 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:78613 |