Time resolved small angle x-ray scattering studies of macromolecular folding

Large biological molecules like proteins and RNA, carry out their functions by folding to well-defined three-dimensional structures. We are interested in the physical interactions that direct this self-assembly process. By combining microfabricated rapid mixers with synchrotron x-ray scattering, we have gained insight into the earliest steps of folding of the Tetrahymena ribozyme, a model for large RNAs. Previous work has shown that the first folding step involves electrostatic relaxation of the molecule. We will discuss a recent series of experiments that identify the tertiary contacts that form from within this compact state.