Iterative phasing for fluctuation X-ray scattering

Significance Fluctuation X-ray scattering is an emerging imaging technique that seeks to overcome the low data-to-parameter ratio encountered in traditional small- and wide-angle X-ray scattering methods. By acquiring a large number of ultrashort X-ray exposures on an ensemble of molecules, this technique produces a dataset that contains structural information far beyond what is obtainable from traditional solution scattering methods without requiring crystallization. However, reconstructing the underlying molecular shape from this data is challenging, as the information in each image is averaged over several molecular orientations. In this article, we introduce a flexible iterative method that can rapidly determine molecular structure from fluctuation scattering data. This allows one to visualize structural details that may be inaccessible through traditional methods. Fluctuation X-ray scattering (FXS) is an extension of small- and wide-angle X-ray scattering in which the X-ray snapshots are taken below rotational diffusion times. This technique, performed using a free electron laser or ultrabright synchrotron source, provides significantly more experimental information compared with traditional solution scattering methods. We develop a multitiered iterative phasing algorithm to determine the underlying structure of the scattering object from FXS data.

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