Protein folding observed by time-resolved synchrotron x-ray scattering. A feasibility study.

A solution to the "protein folding" problem, the successful prediction of tertiary and quaternary protein structure from amino acid or gene sequence, would be a major advance in biology and biotechnology. Knowledge of any intermediate structure between fully unwound and folded would aid folding calculations. The use of high intensity synchrotron x-rays from the SUNY X21 beamline at National Synchrotron Light Source has been investigated as a probe of structural changes during protein folding and unfolding in solution. A temperature jump apparatus was used to study thermally-induced folding and unfolding. Scattering of solutions of myoglobin in the angular range 20 = 1-50 mrad. was measured during temperature jumps between 26 and 76 degrees C. There are clear signs of time/temperature-dependent structural changes, in the small angle region, consistent with those from other equilibrium techniques. Analysis indicates that this experimental technique can be extended to the higher angle region where theoretical calculations indicate more detailed structural information, for example when alpha-helix formation, is present.