Details of Grant 

EPSRC Reference:	EP/J019623/1
Title:	Modelling Carbohydrate Solution Structure Using a Novel Combined Experimental-Computational Strategy
Principal Investigator:	Popelier, Professor P
Other Investigators:	Blanch, Professor EW
Researcher Co-Investigators:
Project Partners:	Gaussian Inc
Department:	Faculty of Biology (do not use)
Organisation:	University of Manchester, The
Scheme:	Standard Research
Starts:	01 July 2012	Ends:	31 May 2016	Value (£):	687,547
EPSRC Research Topic Classifications:	Chemical Biology
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:
Panel History:	Panel Date Panel Name Outcome 18 Apr 2012 EPSRC Physical Sciences Chemistry - April 2012 Announced
Summary on Grant Application Form
Our ability to make new discoveries in biochemistry and to develop new pharmaceuticals, advanced materials, energy sources and foodstuffs is increasingly dependent on our understanding of how biomolecules work at the molecular level. This in turn depends on our understanding of the structure of these biomolecules, and how their structures control their functions. This has been the guiding principle that has resulted in many of the advances in medicine, biology, chemistry and materials science of the last few decades. These advances have owed much to the structural information that has been obtained for proteins and nucleic acids by X-ray crystallography and NMR spectroscopy, and which has revolutionised our view of how life works. Unfortunately, these techniques are far more difficult to apply to the main class of biomolecules, carbohydrates. As a result, even though carbohydrates constitute around 99% of the biomass of our planet and perform an almost limitless number of roles in living systems, from algae to plants to humans, we don't really understand how they work in the same way that we do for proteins and DNA. The lack of definitive data means there is still considerable debate as to how we even define structure in carbohydrate polymers. In order to best capitalise on the great potential of carbohydrates in both science and industry we will have to understand to a much greater level of detail the molecular principles that govern their assembly, organisation and interactions with other molecules. This will require new approaches to studying carbohydrate structure. In order to meet this urgent requirement we will develop a combined computer modelling and spectroscopic lab-based approach to characterising the structures of carbohydrates, from simple sugars to key carbohydrate polymers known to be involved in regulating biological functions. Three components to the project will combine to generate a uniquely incisive new tool for glycobiology. First, high level quantum chemistry calculations will provide highly detailed spectra that are sensitive to all aspects of carbohydrate conformation, so allowing us to identify subtle structural differences. Secondly, as recent work shows that hydration plays an important role in controlling carbohydrate conformation, we will use molecular dynamics simulations to identify which structures are formed by each carbohydrate in the solvated environments in which they are found naturally and how they interact with the water molecules around them. Thirdly, we will measure highly detailed Raman spectra to provide the gold standard benchmarks required to prove that our calculations and modelling are correct. This will also provide us with a rigorous standard against which to validate the novel computer modelling. Although this development of new computational tools will be focused on the structures and behaviour of carbohydrates, the end product will also be widely applicable to all other biomolecules, particularly proteins and nucleic acids. The challenges we will overcome are those faced by researchers attempting to model how other molecules behave, e.g. how stable is the structure? how do its components interact? how do interactions with solvent water or other molecules affect its shape? Because our novel computational tools are generic they will be able to provide new insights into many other areas of research, such as protein-ligand interactions and DNA-drug molecule binding.
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Organisation Website:	http://www.man.ac.uk