Technology that drives new science: 2D IR spectroscopy and
and its application to protein aggregation and drug binding.

2D IR spectroscopy is proving to be a very useful tool for studying molecular structures and their dynamics. It is now being applied in fields ranging from biophysics to the energy sciences. In this talk, I will present our contributions to the technological development of this exciting spectroscopy as well as an application to amyloid fiber formation and drug inhibition. A few years ago, we invented a mid-IR pulse shaper that enabled us to computer generate the 2D IR pulse trains. This device makes data collection faster, more accurate, and enables new capabilities such as phase cycling. Using this method, we can now rapidly scan 2D IR spectra to monitor structural kinetics, which we have done to monitor the aggregation of amylin, which is the polypeptide associated with type 2 diabetes. We will present results in which we have time-resolved the secondary structure of individual residues, providing some of the most detailed information available on fiber formation. Moreover, I will also present our recent work on drug binding, in which we have resolved the binding site and mechanism of a peptide inhibitor that blocks fiber formation. With 2D IR spectroscopy, we obtain an unprecedented level of structural and kinetic detail on systems that are traditionally difficult to study with standard structural biology tools.

| Announcement of Laureates 2011 |