Taylor, R., Cole, J.C., Cosgrove, D.A. et al. (3 more authors) (2012) Development and validation of an improved algorithm for overlaying flexible molecules. Journal of Computer-Aided Molecular Design, 26 (4). 451 - 472.
Abstract
A program for overlaying multiple flexible molecules has been developed. Candidate overlays are generated by a novel fingerprint algorithm, scored on three objective functions (union volume, hydrogen-bond match, and hydrophobic match), and ranked by constrained Pareto ranking. A diverse subset of the best ranked solutions is chosen using an overlay-dissimilarity metric. If necessary, the solutions can be optimised. A multi-objective genetic algorithm can be used to find additional overlays with a given mapping of chemical features but different ligand conformations. The fingerprint algorithm may also be used to produce constrained overlays, in which user-specified chemical groups are forced to be superimposed. The program has been tested on several sets of ligands, for each of which the true overlay is known from protein–ligand crystal structures. Both objective and subjective success criteria indicate that good results are obtained on the majority of these sets.
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © Year The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Alignment; Overlay; Pharmacophore |
Dates: |
|
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 14:49 |
Last Modified: | 23 Apr 2014 08:04 |
Published Version: | http://dx.doi.org/10.1007/s10822-012-9573-y |
Status: | Published |
Publisher: | Springer Netherlands |
Refereed: | Yes |
Identification Number: | 10.1007/s10822-012-9573-y |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:78617 |