Methods in Fiber Diffraction Analysis of Macromolecules

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This award provides funds for the continued development of X-ray fiber diffraction techniques for structural analysis of macromolecular assemblies. Typical such assemblies include virions, other nucleoprotein complexes, and cytoskeletal filaments. The technique has been used for years and has already played a key role in biology through, for example, the discovery of the structure of DNA by Watson and Crick. However, there remain significant challenges with respect to sample preparation and data analysis which these studies will address. The use of X-rays to analyze molecular structure at the atomic level has been key to the recent, rapid advance in our knowledge of the structure of molecules of biological importance. Much of the information has come from crystallographic studies in which the subject molecules are crystallized from solution prior to the analysis. The use of fiber diffraction techniques eliminates the need for this difficult, time consuming, and often impossible task. However, because the methods for sample preparation and analysis of large biological molecules are as yet poorly worked out, the fiber diffraction techniques has not been widely adopted. Progress in development of these methods can be expected to play an important role in understanding the structure of large macromolecular assemblies, many of which are poorly suited to analysis by more conventional analyses.