POCKETSPPI

Discovering and exploiting hidden pockets at protein-protein interfaces

 Coordinatore THE UNIVERSITY OF EDINBURGH 

 Organization address address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL

contact info
Titolo: Ms.
Nome: Angela
Cognome: Noble
Email: send email
Telefono: +44 131 650 9024
Fax: +44 131 650 9023

 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 100˙000 €
 EC contributo 100˙000 €
 Programma FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call FP7-PEOPLE-2010-RG
 Funding Scheme MC-IRG
 Anno di inizio 2011
 Periodo (anno-mese-giorno) 2011-09-01   -   2015-08-31

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF EDINBURGH

 Organization address address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL

contact info
Titolo: Ms.
Nome: Angela
Cognome: Noble
Email: send email
Telefono: +44 131 650 9024
Fax: +44 131 650 9023

UK (EDINBURGH) coordinator 100˙000.00

Mappa


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interfaces    pockets    protein    binding    drug    small    proteins    interactions    ligands    hidden    computational    greatly    molecular    molecule    shape   

 Obiettivo del progetto (Objective)

'Protein-protein interactions play critical roles in normal human physiology, as well as in numerous diseases such as cancers and neurodegenerative disorders. However, identifying small molecule drugs to block protein interactions is a very difficult task. One of the major difficulties is that often the proteins involved are extremely flexible and readily change shape, which greatly complicates efforts to find small molecule ligands of matching shape. In this project, we aim to exploit protein flexibility to create new opportunities for drug discovery.

Interactions between a given pair of proteins commonly requires one or both partners to transiently form pockets that allow selective binding. Therefore, most protein interfaces likely possess many more binding pockets than those apparent in the static picture of a protein structure revealed by crystallographic experiments. We propose to identify these 'hidden' pockets using computational methods. Thus, we will develop and validate molecular simulation methodologies to detect hidden pockets at protein interfaces and assess their small molecule 'druggability' using docking calculations and binding site scoring functions. Such capacity would greatly strengthen the reliability of in silico drug design. We will perform virtual screens to find small molecule ligands binding to hidden pockets in medicinally important proteins such as FcgammaRIIA or PCNA. Finally, we will purchase or synthesize promising ligands and assay their activity against protein targets. These studies will allow us to test the utility of our computational approach in rational drug design.

The objectives of this research are part of a broader program we are currently developing and whose purpose is to provide a comprehensive set of computational/biophysical methods to allow the widespread targeting of seemingly 'undruggable' protein families with small molecules, thereby expanding the scope of modern molecular medicine.'

Altri progetti dello stesso programma (FP7-PEOPLE)

FUNGENCEL (2009)

Functional Genomics of Fatty Acid Desaturases in Caenorhabditis elegans

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INSTOCS (2011)

Incorporating in Numerical Schemes Transition On Curved Surfaces

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BIRDISLAND (2011)

Ecological and Genomic Approaches to Speciation in Island Birds

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