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Details of Grant 

EPSRC Reference: EP/H051759/1
Title: New Multiscale Tools for Protein Physics: Thermal Protein Dynamics in Signalling and Allostery.
Principal Investigator: McLeish, Professor T
Other Investigators:
Pohl, Dr E Cann, Professor M Wilson, Professor MR
Researcher Co-Investigators:
Project Partners:
Department: Chemistry
Organisation: Durham, University of
Scheme: Standard Research
Starts: 01 October 2010 Ends: 31 March 2014 Value (£): 861,489
EPSRC Research Topic Classifications:
Chemical Biology Complex fluids & soft solids
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:
Panel DatePanel NameOutcome
05 May 2010 Physical Sciences Panel- Physics Announced
Summary on Grant Application Form
Proteins are natures molecular machines. Built out of an alphabet of only 24 small molecules joined into long chains, in folded-form they constitute the structures, scaffolds, signalling pathways, transport systems, motors and cargo transporters of the tissues and cells of all living things. Since their exquisitely evolved and precise structures have been elucidated through X-ray scattering, the emphasis has been on understanding how these structures lead to function (such as binding to specific small molecules at special pockets and clefts). More recently however, it has become clear that the constant dynamical excitations of proteins, a natural consequence of a finite-temperature environment, also play a vital role in function. Data from careful thermal analysis, and also from magnetic resonance measurements, have shown how binding events at proteins can change the nature of their internal ceaseless wobbling considerably. Furthermore, recent work by the applicants has shown how mathematical and physical models of proteins can analyse these motions and identify how their changes are used to generate vital signals within protein networks. These control all aspects of cell function, so understanding them is very important in biology.The goal of this project is to build on the initial foundations of coarse-grained protein modelling and link the global models of entire protein molecules to their atomistic structure in a predictive way. The physicists and chemists will work with biologists in validating these new tools on a series of model protein systems. By making tiny changes in the proteins ( mutations ), predictions of the models can be tested by experiments. A particular goal is to use the technique to design a new protein with entirely new allostetric properties that have been engineered into the protein on the basis of the course-grained model. This will demonstrate a potential route to commercialisation of the science in biotechnology.At the end of the project, a systematic analytical tool for global protein dynamics will be available to the community, both academic and industrial.
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