Abstract by Isabella James
Chemistry and Biochemistry
Measuring the Folding Stability of the Proteome
Correct folding is essential to each proteins’ function; incorrectly folded or aggregated proteins can lead to aging, Alzheimer’s or other diseases. Thermodynamic study of protein folding is very informative, but traditionally requires purified protien. Studying the thermodynamic folding stability within the mixture of the cell is a key step required to understand in vivo folding quality and the etiology of aging and disease. We are currently developing a method to measure the folding stabilities of many proteins within the complex mixture of the proteome simultaneously. We denature the proteins with different concentrations of guanidine, allowing us to covelantly modify the newly exposed regions of the protein. We can then measure the modified proteins using mass spectrometry. This allows us to calculate denaturation curves and thermodynamic stabilities for many proteins at once. In the future, we will apply this method to studying the folding stability of the proteome in diseased states.