Abstract
Single-particle electron cryomicroscopy (cryo-EM) is an increasingly popular technique for elucidating the three-dimensional structure of proteins and other biologically significant complexes at near-atomic resolution. It is an imaging method that does not require crystallization and can capture molecules in their native states. In single-particle cryo-EM, the three-dimensional molecular structure needs to be determined from many noisy two-dimensional tomographic projections of individual molecules, whose orientations and positions are unknown. The high level of noise and the unknown pose parameters are two key elements that make reconstruction a challenging computational problem. Even more challenging is the inference of structural variability and flexible motions when the individual molecules being imaged are in different conformational states. This review discusses computational methods for structure determination by single-particle cryo-EM and their guiding principles from statistical inference, machine learning, and signal processing that also play a significant role in many other data science applications.
🔬 Techniques
🧪 Sample Preparation
🔬 Cell Lines
🏭 Microscope Brands
📷 Detectors
💻 Software Details
🏛️ Research Organizations (ROR)
Affiliated research institutions:
📊 Figures
Figure 1
A cryo-EM micrograph of PaaZ protein particles. A , the entire micrograph, depicting a specimen area of 434 u00d7 434 nm with a pixel size of 1.06u00c5. The field contains about 220 PaaZ particles alo...
Figure 2
Model of image formation by defocus contrast. A , a projection of the experimental density map of PaaZ. B , projection of the map at the best-match orientation determined from a particle image. C , th...
Figure 3
Particle images and 2D class averages. Left , a gallery of particle images extracted from micrographs. The experimental images are shown cropped to boxes of 256 pixels of 1.06u00c5 per pixel, and cont...
Figure 4
The last step in structure determination: fit of an atomic model to the PaaZ reconstruction. A , overview of the PaaZ model, with ribbons denoting the folding of the polypeptide chain. To give an idea...
Figure images are served from the NIH/NLM PubMed Central Open Access Subset or Europe PMC; copyright remains with the publishers and authors.
💬 Discussion
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