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Real-Time Observation of Biological Reactions Using Femtosecond 2D-IR Spectroscopy – Introducing SPRITES (Introducing SPRITES)
Start date: 01 Aug 2008, End date: 31 Jul 2012 PROJECT  FINISHED 

A fundamental question facing physical chemistry and biology is to determine the basic mechanisms by which biological molecules react and change structure. Ultrafast two dimensional infrared (2D-IR) spectroscopy has emerged as an exciting new tool for probing the structure and dynamics of bio-systems. This proposal is the first concerted application of transient 2D-IR spectroscopy to answer pressing questions relating to reactions of biological systems. The unique combination of ultrafast time resolution and structural insight makes 2D-IR the perfect platform to observe real-time structure changes during reactions. We will exploit this ability by developing SPRITES – Structure changes in Protein Reactions via Infrared Time Evolution Spectroscopy. We will trigger reactions in peptide and enzyme systems and use 2D-IR as a time-delayed probe of molecular structure to follow them in unprecedented real-time detail. This ambitious project will be split into three stages for reasons of risk management: In stage one, simple photochemical reactions of model compounds of the hydrogenase enzyme active site will be initiated and the structural evolution of the reactants followed using 2D-IR. In stage two, the novel pH-jump SPRITES technique will be developed to study peptide folding reactions. These experiments will lead to a “molecular movie” of a folding peptide in a natural environment, representing a unique scientific development. The final stage of the project will use pH-jump SPRITES to initiate and observe the reaction of a complete hydrogenase enzyme. This ambitious final stage will yield unprecedented insight into the mechanisms of biological reactions. The purpose of the proposal is to assist the PI in consolidating the independence gained through the award of a prestigious EPSRC Fellowship. The proposal seeks funding to create a research team of two postdoctoral research associates and two PhD students. This team will be managed and directed by the PI.
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