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Details of Grant 

EPSRC Reference: GR/S61515/01
Title: Studies of Delocalized Binding Energy of Ligands to Receptors
Principal Investigator: Williams, Professor D
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: University of Cambridge
Scheme: Standard Research (Pre-FEC)
Starts: 01 October 2003 Ends: 30 September 2004 Value (£): 71,049
EPSRC Research Topic Classifications:
Analytical Science Biological & Medicinal Chem.
Chemical Biology
EPSRC Industrial Sector Classifications:
Pharmaceuticals and Biotechnology
Related Grants:
Panel History:  
Summary on Grant Application Form
In prior work, we have established that simple receptor systems can tightening their internal structures to increase their stability upon ligand binding. This increased stability, associated with the positive cooperative binding, is characterised by increased exothermicity and a cost in entropy. We have also shown, by means of a thermodynamic cycle, that the increased stability of the receptor system when the ligand is bound necessarily leads to increased ligand binding energy. We now wish to extend our work to show that protein receptors may use these effects to provide ligand binding energy. We will use electrospray mass spectrometry, in conjunction with deuterium exchange experiments, to uncover these proposed tightening effects. The tightened regions of the protein receptors will be determined by pepsin digestion of the receptors. Negatively cooperative binding will be probed by the same methodology, with the expectation that structural loosening of the receptors will be observed.
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Organisation Website: http://www.cam.ac.uk