A novel graph-based method for targeted ligand-protein fitting

2.50
Hdl Handle:
http://hdl.handle.net/10547/346403
Title:
A novel graph-based method for targeted ligand-protein fitting
Authors:
Hannaford, Gareth James
Abstract:
The determination of protein binding sites and ligand -protein fitting are key to understanding the functionality of proteins, from revealing which ligand classes can bind or the optimal ligand for a given protein, such as protein/ drug interactions. There is a need for novel generic computational approaches for representation of protein-ligand interactions and the subsequent prediction of hitherto unknown interactions in proteins where the ligand binding sites are experimentally uncharacterised. The TMSite algorithms read in existing PDB structural data and isolate binding sites regions and identifies conserved features in functionally related proteins (proteins that bind the same ligand). The Boundary Cubes method for surface representation was applied to the modified PDB file allowing the creation of graphs for proteins and ligands that could be compared and caused no loss of geometric data. A method is included for describing binding site features of individual ligands conserved in terms of spatial relationships allowed identification of 3D motifs, named fingerprints, which could be searched for in other protein structures. This method combine with a modification of the pocket algorithm allows reduced search areas for graph matching. The methods allow isolation of the binding site from a complexed protein PDB file, identification of conserved features among the binding sites of individual ligand types, and search for these features in sequence data. In terms of spatial conservation create a fingerprint ofthe binding site that can be sought in other proteins of/mown structure, identifYing putative binding sites. The approach offers a novel and generic method for the identification of putative ligand binding sites for proteins for which there is no prior detailed structural characterisation of protein/ ligand interactions. It is unique in being able to convert PDB data into graphs, ready for comparison and thus fitting of ligand to protein with consideration of chemical charge and in the future other chemica! properties.
Citation:
Hannaford, G.J. (2008) 'A novel graph-based method for targeted ligand-protein fitting'. MPhil thesis. University of Bedfordshire.
Publisher:
University of Bedfordshire
Issue Date:
Aug-2008
URI:
http://hdl.handle.net/10547/346403
Type:
Thesis or dissertation
Language:
en
Description:
A thesis submitted to the Faculty of Creative Arts, Technologies & Science, University of Bedfordshire, in partial & fulfilment of the requirements for the degree of Master of Philosophy.
Appears in Collections:
Masters e-theses

Full metadata record

DC FieldValue Language
dc.contributor.authorHannaford, Gareth Jamesen
dc.date.accessioned2015-03-09T10:59:44Zen
dc.date.available2015-03-09T10:59:44Zen
dc.date.issued2008-08en
dc.identifier.citationHannaford, G.J. (2008) 'A novel graph-based method for targeted ligand-protein fitting'. MPhil thesis. University of Bedfordshire.en
dc.identifier.urihttp://hdl.handle.net/10547/346403en
dc.descriptionA thesis submitted to the Faculty of Creative Arts, Technologies & Science, University of Bedfordshire, in partial & fulfilment of the requirements for the degree of Master of Philosophy.en
dc.description.abstractThe determination of protein binding sites and ligand -protein fitting are key to understanding the functionality of proteins, from revealing which ligand classes can bind or the optimal ligand for a given protein, such as protein/ drug interactions. There is a need for novel generic computational approaches for representation of protein-ligand interactions and the subsequent prediction of hitherto unknown interactions in proteins where the ligand binding sites are experimentally uncharacterised. The TMSite algorithms read in existing PDB structural data and isolate binding sites regions and identifies conserved features in functionally related proteins (proteins that bind the same ligand). The Boundary Cubes method for surface representation was applied to the modified PDB file allowing the creation of graphs for proteins and ligands that could be compared and caused no loss of geometric data. A method is included for describing binding site features of individual ligands conserved in terms of spatial relationships allowed identification of 3D motifs, named fingerprints, which could be searched for in other protein structures. This method combine with a modification of the pocket algorithm allows reduced search areas for graph matching. The methods allow isolation of the binding site from a complexed protein PDB file, identification of conserved features among the binding sites of individual ligand types, and search for these features in sequence data. In terms of spatial conservation create a fingerprint ofthe binding site that can be sought in other proteins of/mown structure, identifYing putative binding sites. The approach offers a novel and generic method for the identification of putative ligand binding sites for proteins for which there is no prior detailed structural characterisation of protein/ ligand interactions. It is unique in being able to convert PDB data into graphs, ready for comparison and thus fitting of ligand to protein with consideration of chemical charge and in the future other chemica! properties.en
dc.language.isoenen
dc.publisherUniversity of Bedfordshireen
dc.subjectC700 Molecular Biology, Biophysics and Biochemistryen
dc.subjectligand bindingen
dc.subjectprotein bindingen
dc.subjectprotein-ligand interactionsen
dc.subjectgraph matchingen
dc.titleA novel graph-based method for targeted ligand-protein fittingen
dc.typeThesis or dissertationen
This item is licensed under a Creative Commons License
Creative Commons
All Items in UOBREP are protected by copyright, with all rights reserved, unless otherwise indicated.