Cryo-EM, XFELs and the structure conundrum in structural biology

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Single-particle techniques offer an unprecedented opportunity to understand the role of structural variability in biological function. They also call into question the meaning of ‘a structure’ and its relevance to function.

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Fig. 1: Hypersurface representing all possible conformations of a molecule.
Fig. 2: Experimentally determined conformational motions and energy landscape of a ribosome.
Fig. 3: Four frames of a 50-frame movie showing the conformational changes in the PR772 virus.

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Acknowledgements

I am indebted to my colleagues at the University of Wisconsin Milwaukee for many discussions, and to J. Frank, A. Singharoy for valuable comments on the manuscript. The research conducted at the University of Wisconsin Milwaukee was supported by the US Department of Energy, Office of Science, Basic Energy Sciences under award DE-SC0002164 (algorithm design and development), and by the US National Science Foundation under awards STC 1231306 (numerical trial models and data analysis) and 1551489 (underlying analytical models).

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Correspondence to Abbas Ourmazd.

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