| EPSRC Reference: |
GR/S00842/01 |
| Title: |
Development of CRYSTALLOHYDRODYNAMICS for the analysis of antibody conformation under physiological conditions |
| Principal Investigator: |
Harding, Professor SE |
| Other Investigators: |
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| Researcher Co-Investigators: |
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| Project Partners: |
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| Department: |
Sch of Biosciences |
| Organisation: |
University of Nottingham |
| Scheme: |
Standard Research (Pre-FEC) |
| Starts: |
01 July 2003 |
Ends: |
30 September 2006 |
Value (£): |
278,877
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| EPSRC Research Topic Classifications: |
| Chemical Biology |
Complex fluids & soft solids |
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| EPSRC Industrial Sector Classifications: |
| No relevance to Underpinning Sectors |
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| Panel History: |
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Summary on Grant Application Form |
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1. Take the state of the art theories for representing the overall conformation of a globular macromolecule - such as an antibody domain - in terms of the axial ratios a/b, b/c of a general surface inertial ellipsoid of semi axes a,b,c. Do the same for working out the complete hydrodynamic properties of ellipsoids of defined (a/b, b/c) and for bead-shell models of defined bead coordinates. Choose the IgG2 class of antibody. Fit the known crystal structure (stored a pdb file) of the Fab and Fc domains to surface ellipsoids (in terms of a bead-shell array). Measure and fit a bead shell model)2. Check the previously measured sedimentation coefficient, s, for the domains and then measure for the first time an accurate intrinsic viscosity [eta] and harmonic mean rotational relaxation time, tau. Combine this data with 2 to evaluate the molecular hydration of the domains. Then work out a weighted average hydration for the intact molecule, delta. Measure s, [eta] and tau for the intact antibody. Use this, together with the delta, to model the orientation of domains using bead-shell models for the intact antibody, under different solvent conditions.3. Repeat for a range of engineered IgG based antibodies and also IgE to obtain a complete dossier for the IgG and IgE classes of antibody domain orientation as a function of solution and liganded conditions.
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Key Findings |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Potential use in non-academic contexts |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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Impacts |
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| Description |
This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk |
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| Date Materialised |
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Sectors submitted by the Researcher |
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This information can now be found on Gateway to Research (GtR) http://gtr.rcuk.ac.uk
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| Project URL: |
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| Further Information: |
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| Organisation Website: |
http://www.nottingham.ac.uk |