2.50
Hdl Handle:
http://hdl.handle.net/10547/294685
Title:
Docking of flexible molecules using multiscale ligand representations
Authors:
Glick, Meir; Grant, Guy H.; Richards, W. Graham
Abstract:
Here, we present a fully automated, efficient docking methodology that does not require any a priori knowledge about the location of the binding site or function of the protein. The method relies on a multiscale concept where we deal with a hierarchy of models generated for the potential ligand. The models are created using the k-means clustering algorithm. The method was tested on seven protein−ligand complexes. In the largest complex, human immunodeficiency virus reverse transcriptase/nevirapin, the root mean square deviation value when comparing our results to the crystal structure was 0.29 Å. We demonstrate on an additional 25 protein−ligand complexes that the methodology may be applicable to high throughput docking. This work reveals three striking results. First, a ligand can be docked using a very small number of feature points. Second, when using a multiscale concept, the number of conformers that require to be generated can be significantly reduced. Third, fully flexible ligands can be treated as a small set of rigid k-means clusters.
Citation:
Glick, M., Grant, G.H. and Richards, W.G. (2002) 'Docking of flexible molecules using multiscale ligand representations', Journal of Medicinal Chemistry, 45(21),pp.4639-4646.
Publisher:
American Chemical Society
Journal:
Journal of Medicinal Chemistry
Issue Date:
2002
URI:
http://hdl.handle.net/10547/294685
DOI:
10.1021/jm020830i
Additional Links:
http://pubs.acs.org/doi/abs/10.1021/jm020830i
Type:
Article
Language:
en
ISSN:
0022-2623; 1520-4804
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorGlick, Meiren_GB
dc.contributor.authorGrant, Guy H.en_GB
dc.contributor.authorRichards, W. Grahamen_GB
dc.date.accessioned2013-06-26T14:53:35Z-
dc.date.available2013-06-26T14:53:35Z-
dc.date.issued2002-
dc.identifier.citationGlick, M., Grant, G.H. and Richards, W.G. (2002) 'Docking of flexible molecules using multiscale ligand representations', Journal of Medicinal Chemistry, 45(21),pp.4639-4646.en_GB
dc.identifier.issn0022-2623-
dc.identifier.issn1520-4804-
dc.identifier.doi10.1021/jm020830i-
dc.identifier.urihttp://hdl.handle.net/10547/294685-
dc.description.abstractHere, we present a fully automated, efficient docking methodology that does not require any a priori knowledge about the location of the binding site or function of the protein. The method relies on a multiscale concept where we deal with a hierarchy of models generated for the potential ligand. The models are created using the k-means clustering algorithm. The method was tested on seven protein−ligand complexes. In the largest complex, human immunodeficiency virus reverse transcriptase/nevirapin, the root mean square deviation value when comparing our results to the crystal structure was 0.29 Å. We demonstrate on an additional 25 protein−ligand complexes that the methodology may be applicable to high throughput docking. This work reveals three striking results. First, a ligand can be docked using a very small number of feature points. Second, when using a multiscale concept, the number of conformers that require to be generated can be significantly reduced. Third, fully flexible ligands can be treated as a small set of rigid k-means clusters.en_GB
dc.language.isoenen
dc.publisherAmerican Chemical Societyen_GB
dc.relation.urlhttp://pubs.acs.org/doi/abs/10.1021/jm020830ien_GB
dc.rightsArchived with thanks to Journal of Medicinal Chemistryen_GB
dc.titleDocking of flexible molecules using multiscale ligand representationsen
dc.typeArticleen
dc.identifier.journalJournal of Medicinal Chemistryen_GB
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