4.6 Article

High-resolution structure of viruses from random diffraction snapshots

出版社

ROYAL SOC
DOI: 10.1098/rstb.2013.0326

关键词

macromolecular assemblies; symmetry; X-ray lasers; manifold embedding; dimensionality reduction

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资金

  1. US Department of Energy, Office of Science, Basic Energy Sciences [DE-FG02-09ER16114]
  2. US National Science Foundation [MCB-1240590, CCF-1013278, CNS-0968519, STC 1231306]
  3. UWM Research Growth Initiative

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The advent of the X-ray free-electron laser (XFEL) has made it possible to record diffraction snapshots of biological entities injected into the X-ray beam before the onset of radiation damage. Algorithmic means must then be used to determine the snapshot orientations and thence the three-dimensional structure of the object. Existing Bayesian approaches are limited in reconstruction resolution typically to 1/10 of the object diameter, with the computational expense increasing as the eighth power of the ratio of diameter to resolution. We present an approach capable of exploiting object symmetries to recover three-dimensional structure to high resolution, and thus reconstruct the structure of the satellite tobacco necrosis virus to atomic level. Our approach offers the highest reconstruction resolution for XFEL snapshots to date and provides a potentially powerful alternative route for analysis of data from crystalline and nano-crystalline objects.

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