Abstract

Single particle cryo-electron microscopy is currently poised to produce high-resolution structures of many biological assemblies, but several pitfalls can trap the unwary. This critique highlights one problem that is particularly relevant when smaller structures are being studied. It is known as “Einstein from noise,” in which the experimenter honestly believes they have recorded images of their particles, whereas in reality, most if not all of their data consist of pure noise. Selection of particles using cross-correlation methods can then lead to 3D maps that resemble the model used in the initial selection and provide the illusion of progress. Suggestions are given about how to circumvent the problem.

Keywords

IllusionEinsteinNoise (video)Particle (ecology)Single particle analysisMicroscopyCryo-electron microscopySelection (genetic algorithm)Statistical physicsElectron microscopeResolution (logic)PhysicsComputer scienceTheoretical physicsOpticsArtificial intelligenceBiologyClassical mechanicsNuclear magnetic resonance

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Publication Info

Year
2013
Type
letter
Volume
110
Issue
45
Pages
18037-18041
Citations
223
Access
Closed

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Richard A. Henderson (2013). Avoiding the pitfalls of single particle cryo-electron microscopy: Einstein from noise. Proceedings of the National Academy of Sciences , 110 (45) , 18037-18041. https://doi.org/10.1073/pnas.1314449110

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DOI
10.1073/pnas.1314449110