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Details of Grant 

EPSRC Reference: GR/N10950/01
Title: ASYMETRIC CHARGE NEUTRALISATION IN PROTEIN INDUCED DNA-BENDING
Principal Investigator: Allemann, Professor RK
Other Investigators:
Researcher Co-Investigators:
Project Partners:
Department: School of Chemistry
Organisation: University of Birmingham
Scheme: Standard Research (Pre-FEC)
Starts: 03 July 2000 Ends: 02 September 2003 Value (£): 62,941
EPSRC Research Topic Classifications:
Biological & Medicinal Chem.
EPSRC Industrial Sector Classifications:
Pharmaceuticals and Biotechnology No relevance to Underpinning Sectors
Related Grants:
Panel History:  
Summary on Grant Application Form
Non-covalent interactions between nucleic acids and proteins govern biological process such as replication, recombination, and transcription. The formation of protein-DNA complexes are often accompanied by significant conformational changes of both reaction partners in order to ensure an optimal fit. While there is increasing evidence suggesting that assymmetic charge neutralisation is one of the mechanisms used by proteins to induce DNA bending, little is known about the thermodynamic parameters which control such association reactions. In order to determine the contribution of charge neutralisation to the overall stability of the DNA complexes of MEF-2C, the free energy of complex formation will be determined by electrophoretic mobility shift assays for complexes in which individual charge interactions are removed by replacing either negatively charged phosphodiester linkages with uncharged methylphosphonates or positively charged residues of MEF-2C with uncharged ones. In addition to providing information about the thermodynamics of charge neutralisation, such an approach should also allow us to measure the free energy required to bend the free DNA into the conformation which it adopts in the MEF-2C complex, thereby providing a thermodynamic bendability scale of the oligonucleotides.
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Organisation Website: http://www.bham.ac.uk