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UBC Theses and Dissertations

The effect of osmolytes on protein folding Hadizadeh, Shirin


Living cells are composed of a variety of biological macromolecules such as nucleic acid, metabolites, proteins and cytoskeletal filaments as well as other particles. The fraction of the cellular interior volume that is taken by these biomolecules is about 30%, leading to a highly crowded environment. Biomolecules present in an extremely dense environment inside a cell have a completely different set of kinetic and thermodynamic behavior than in a test tube. Therefore comprehending the effect of crowding conditions on biological molecules is crucial to broad research fields such as biochemical, medical and pharmaceutical sciences. Experimentally, we are able to mimic such crowded environments; which are of more physiological relevance, by adding high concentrations of synthetic macromolecules into uncrowded buffers. Theoretically, very little attention has been paid to the effects of the dense cellular cytoplasm on biological reactions. The purpose of this work is to investigate analytically the effects of crowding agents on protein folding and stability. We present a new parameter as the measure of the polymer size, which will substitute the traditional measurements of the radius of gyration of the polymer and the end to end distance of a polymeric chain. Using this quantity we derive an expression for the free energy of the polymer which can easily be generalized to provide the free energy of a protein. This mechanism enables us to study the effect of crowding on folding and stability of a protein. The stabilization effects of the crowding particles depend on the concentration and the size of the crowders and also the type of the crowding particles that are present in the system. In our calculations the type of the crowders is controlled by the energetic parameter between the protein and surrounding macromolecules.

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