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Role of macromolecular crowding on the structure and stability of proteins

The inside of cells is highly packed due to the large amount of macromolecules (e.g. proteins) present (see image below). This gives rise to an excluded volume effect, which effectively compresses proteins, reducing their average dimensions and favouring their native folded states. This effect is known as macromolecular crowding, and it is increasingly accepted that it plays a key role in determining biomolecular structure and interactions in normal and pathological cellular processes. The self-crowding of the regulatory protein calmodulin will be investigated in an aqueous environment, and how it affects its native structure and thermal stability. The effects of protein concentration, ionic strength, pH, temperature and pressure will be characterised in detail using molecular and Brownian dynamics simulations. The data generated will provide a molecular rationale for small angle neutron scattering (SANS) and small angle X-ray scattering (SAXS) experiments that are being carried out by collaborators at the Australian Nuclear Science and Technology Organisation (ANSTO) in Sydney and Gumna University in Japan.

Model of the crowded bacterial cell environment with more than one thousand protein molecules normally found in the cytoplasm
Model of the crowded bacterial cell environment with more than one thousand protein molecules normally found in the cytoplasm. Taken from from McGuffee & Elcock (2010) PLoS Comput. Biol. 6: e1000694.