2.50
Hdl Handle:
http://hdl.handle.net/10547/294699
Title:
Identification of ligand binding sites on proteins using a multi-scale approach
Authors:
Glick, Meir; Robinson, Daniel D.; Grant, Guy H.; Richards, W. Graham
Abstract:
Identification of a ligand binding site on a protein is pivotal to drug discovery. To date, no reliable and computationally feasible general approach to this problem has been published. Here we present an automated efficient method for determining binding sites on proteins for potential ligands without any a priori knowledge. Our method is based upon the multiscale concept where we deal with a hierarchy of models generated using a k-means clustering algorithm for the potential ligand. This is done in a simple approach whereby a potential ligand is represented by a growing number of feature points. At each increasing level of detail, a pruning of potential binding site is performed. A nonbonding energy function is used to score the interactions between molecules at each step. The technique was successfully employed to seven protein−ligand complexes. In the current paper we show that the algorithm considerably reduces the computational effort required to solve this problem. This approach offers real opportunities for exploiting the large number of structures that will evolve from structural genomics.
Citation:
Glick, M., Robinson, D.D., Grant, G.H. and Richards, W.G. (2002) 'Identification of ligand binding sites on proteins using a multi-scale approach', Journal of the American Chemical Society, 124(10),pp.2337-2344.
Publisher:
American Chemical Society
Journal:
Journal of the American Chemical Society
Issue Date:
2002
URI:
http://hdl.handle.net/10547/294699
DOI:
10.1021/ja016490s
Additional Links:
http://pubs.acs.org/doi/abs/10.1021/ja016490s
Type:
Article
Language:
en
ISSN:
0002-7863; 1520-5126
Appears in Collections:
Cell and Cryobiology Research Group

Full metadata record

DC FieldValue Language
dc.contributor.authorGlick, Meiren_GB
dc.contributor.authorRobinson, Daniel D.en_GB
dc.contributor.authorGrant, Guy H.en_GB
dc.contributor.authorRichards, W. Grahamen_GB
dc.date.accessioned2013-06-26T15:18:47Z-
dc.date.available2013-06-26T15:18:47Z-
dc.date.issued2002-
dc.identifier.citationGlick, M., Robinson, D.D., Grant, G.H. and Richards, W.G. (2002) 'Identification of ligand binding sites on proteins using a multi-scale approach', Journal of the American Chemical Society, 124(10),pp.2337-2344.en_GB
dc.identifier.issn0002-7863-
dc.identifier.issn1520-5126-
dc.identifier.doi10.1021/ja016490s-
dc.identifier.urihttp://hdl.handle.net/10547/294699-
dc.description.abstractIdentification of a ligand binding site on a protein is pivotal to drug discovery. To date, no reliable and computationally feasible general approach to this problem has been published. Here we present an automated efficient method for determining binding sites on proteins for potential ligands without any a priori knowledge. Our method is based upon the multiscale concept where we deal with a hierarchy of models generated using a k-means clustering algorithm for the potential ligand. This is done in a simple approach whereby a potential ligand is represented by a growing number of feature points. At each increasing level of detail, a pruning of potential binding site is performed. A nonbonding energy function is used to score the interactions between molecules at each step. The technique was successfully employed to seven protein−ligand complexes. In the current paper we show that the algorithm considerably reduces the computational effort required to solve this problem. This approach offers real opportunities for exploiting the large number of structures that will evolve from structural genomics.en_GB
dc.language.isoenen
dc.publisherAmerican Chemical Societyen_GB
dc.relation.urlhttp://pubs.acs.org/doi/abs/10.1021/ja016490sen_GB
dc.rightsArchived with thanks to Journal of the American Chemical Societyen_GB
dc.titleIdentification of ligand binding sites on proteins using a multi-scale approachen
dc.typeArticleen
dc.identifier.journalJournal of the American Chemical Societyen_GB
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