Protein folding

Proteins are known to adopt specific (but dynamic) three-dimensional structures that allow them to carry out their function.  It is well recognized that this process doesn’t occur by a random search but is instead a biased search.  We are interested in understanding the factors that guide the protein to the correct structure or set of structures.

As part of efforts toward understanding this process we are interested in obtaining structural snapshots of the earliest stages of a protein folding reaction.  Over the past few years we have been focusing on using spectroscopic probes monitoring the geometric and hydrodynamic dimensions of a protein in real time during a folding reaction.  Two complementary experiment techniques that we use and find promising are time-resolved Forster resonant energy transfer (trFRET) and small-angle x-ray scattering (SAXS).  These techniques, especially when combined with our custom microsecond microfluidic mixing techniques, reveal information on the point-to-point distance distributions (trFRET) and low-resolution structural information about partially folded intermediates that transiently populate as the protein folds to the native state.