Dissecting the molecular mechanisms of protecting and denaturing osmolytes on protein stability.

Extreme environments place severe physicochemical constraints on biological systems and significant perturbations to water.Biological organisms have adapted to environmental niches through a number of mechanisms. One important strategy involves the accumulation of organic solutes in the cell. Of particular interest to our group are the small organic molecules trimethylamine-N-oxide (TMAO) and urea. With NIMROD’s increased flux and developments in structural refinement we are now ideally placed to explore this fascinating system. Our aim is to study the hydration and association of a simple tri-peptide in binary and tertiary solutions of TMAO, urea and water. This will allows us to reveal the molecular mechanisms of protein (de)stabilisation of these important co-solutes, including determining if urea’s affinity for the tri-peptide is reduced in the presence of TMAO.