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Details of Grant 

EPSRC Reference: GR/S67388/01
Title: Single Biomolecule Dynamical Spectroscopy: Simulation and Experiment
Principal Investigator: McLeish, Professor T
Other Investigators:
Smith, Professor D A M Adolf, Dr D
Researcher Co-Investigators:
Project Partners:
Department: Physics and Astronomy
Organisation: University of Leeds
Scheme: Standard Research (Pre-FEC)
Starts: 01 July 2003 Ends: 30 June 2004 Value (£): 74,366
EPSRC Research Topic Classifications:
Chemical Biology
EPSRC Industrial Sector Classifications:
No relevance to Underpinning Sectors
Related Grants:
Panel History:  
Summary on Grant Application Form
Protein folding and unfolding urgently requires both new experimental and theoretical/simulation techniques that respect the high dimensionality of the folding space (or high number of degrees of freedom) to make progress. We propose a pilot project to explore novel mechanical unfolding/folding experiments made alongside interpretative simulations. Informed by existing single molecule mechanical unfolding at Leeds, and by the expertise in interpreting frequency-dependent linear rheology in terms of polymer structure, we will develop and apply an oscillatory spectroscopy to concatemers of proteins, as well as to model bioheteropolymers such as dextran. The amplitude and phase shift of the single-molecule compliance as a function of mean strain level and frequency will provide an unprecedentedly rich measure of the folding landscape. The simulations will run at both single and united-atom levels, and will concentrate on interpreting the large phase-shifts in the oscillatory signals expected when intermediate states are present on the unfoldign pathway, as well as guiding the choice of experiments. The experiment-simulation comparison will guide the development of a new highdimensional approach to protein-folding devised in the Leeds group.
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Organisation Website: http://www.leeds.ac.uk