Cottrell, S.J., Gillet, V.J. and Taylor, R. (2006) Incorporating partial matches within multiobjective pharmacophore identification. Journal of Computer-Aided Molecular Design, 20 (12). 735 - 749.
Abstract
This paper describes the extension of our earlier multiobjective method for generating plausible pharmacophore hypotheses to incorporate partial matches. Diverse sets of molecules rarely adopt exactly the same binding mode, and so allowing the identification of partial matches allows our program to be applied to larger and more diverse datasets. The method explores the conformational space of a series of ligands simultaneously with their alignment using a multiobjective genetic algorithm (MOGA). The principles of Pareto ranking are used to evolve a diverse set of pharmacophore hypotheses that are optimised on conformational energy of the ligands, the goodness of the overlay and the volume of the overlay. A partial match is defined as a pharmacophoric feature that is present in at least two, but not all, of the ligands in the set. The number of ligands that map to a given pharmacophore point is taken into account when evaluating an overlay. The method is applied to a number of test cases extracted from the Protein Data Bank (PDB) where the true overlay is known.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2006 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; Molecular alignment; MOGA; Multiobjective optimisation; Multiobjective genetic algorithm; Partial matches. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Social Sciences (Sheffield) > Information School (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 22 Apr 2014 15:23 |
Last Modified: | 23 Apr 2014 08:03 |
Published Version: | http://dx.doi.org/10.1007/s10822-006-9086-7 |
Status: | Published |
Publisher: | Kluwer Academic Publishers |
Refereed: | Yes |
Identification Number: | 10.1007/s10822-006-9086-7 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:78608 |