Details of Grant 

EPSRC Reference:	GR/R86102/01
Title:	Insights into enzyme catalysed hydrogen tunneling at the atomic level using computational chemistry.
Principal Investigator:	Sutcliffe, Professor M
Other Investigators:	Scrutton, Professor NS Mulholland, Professor AJ
Researcher Co-Investigators:
Project Partners:
Department:	Chemistry
Organisation:	University of Leicester
Scheme:	Standard Research (Pre-FEC)
Starts:	01 November 2002	Ends:	31 October 2005	Value (£):	149,103
EPSRC Research Topic Classifications:	Catalysis & enzymology Chemical Biology
EPSRC Industrial Sector Classifications:	No relevance to Underpinning Sectors
Related Grants:	GR/R86119/01
Panel History:
Summary on Grant Application Form
Hydrogen transfer reactions are essential to life-the majority of enzymes catalyse the transfer of hydrogen in some form (proton, hydride transfer or radical transfer). Correct theoretical treatment of these reactions is therefore pivotal to our understanding of biological catalysis at the atomic level. Our world leading pioneering work in this exciting emerging area has established the generic nature of H-tunnelling in biological systems-in many cases enzyme catalysed H-transfer involves quantum mechanical tunnelling. Further, we have established that the degree of H-tunnelling, and the efficiency of the reaction, is strongly affected by the protein environment. We have developed a number of enzyme systems that catalyse common reactions in biology for which we have acquired data supporting tunnelling and high resolution X-ray structures. Our novel studies raise a number of interesting and important issues including: (i) how enzymes achieve quantum tunnelling and how the reaction is affected by protein dynamics, (ii) how different substrates affect the potential energy surface and tunnelling characteristics in a given enzyme, (iii) how site-directed mutagenesis compromises the reaction, and (iv) the role of preorganisation of the enzyme-substrate complex in reaction kinetics. We will address these key issues by building on our earlier computational studies, using combined quantum mechanical/molecular mechanical methods to model the reactions within these enzymes. We will determine reaction paths and kinetic isotope effects. In conjunction with our experimental work, this will develop further a new conceptual framework for enzyme catalysed reactions, giving deeper insight into how efficient hydrogen transfer is achieved.
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Organisation Website:	http://www.le.ac.uk