Protein folding, structure

The mechanism of protein folding is poorly understood. What is the nature of folding intermediates, how do proteins with low sequence homology fold to similar structures and what are the determinants that control correct folding rather than misfolding that may lead to protein aggregation and neurodegerative diseases in vivo. How do dynamics in the unfolded state control the folding process. These are the questions being addressed in this laboratory.

The long-term goal of the protein folding work is to understand the nature of the intermediate structures on the unfolding and refolding pathways. Work in the laboratory uses site-directed mutagenesis and techniques such as 19F and proton NMR, circular dichroism, state-of–the-art fluorescence measurements and other biophysical methods. Of particular interest are methods that allow determination of the time dependence of motions in native and unfolded proteins. A variety of proteins are used to address these questions.