Novel tools to map allosteric networks in proteins.

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Proteins are a class of molecules that provides the majority of essential cellular functions such as catalysis, recognition and transport. These functions require binding of the protein to a 'target' molecule. Binding and the activity of the associated function are largely regulated by the concentration of the involved molecules. However, there are additional regulatory mechanisms in proteins; an important one is 'allostery', in which binding of an (additional) 'effector' molecule changes the activity of the protein towards the target molecule. Binding of target and effector molecule occurs at different sites on the protein surface. The allosteric effect can modulate (enhance/reduce) either target molecule binding or subsequent processing (e.g. enzymatic reaction). The detailed mechanism of allosteric regulation in proteins is largely unknown. We know that the information (signal) of the effector binding event has to cross the protein structure to affect the target site. A plausible assumption is that effector binding induces a 'chain' of conformational changes. The aim of the present project is to detect those pathways within protein structures that transmit the effector signal. Owing to the dynamic nature of proteins, we will run molecular simulations to sample a large number of protein conformations. We will analyse correlated conformational changes within the conformational ensembles to follow the signal transmission at the atomistic level.