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J Struct Biol. 2013 Sep;183(3):377-388. doi: 10.1016/j.jsb.2013.07.005. Epub 2013 Jul 17.

Likelihood-based classification of cryo-EM images using FREALIGN.

Author information

1
National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
2
Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA.
3
Department of Biochemistry, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA; Howard Hughes Medical Institute, Brandeis University, MS029, 415 South Street, Waltham, MA 02454, USA. Electronic address: niko@grigorieff.org.

Abstract

We describe an implementation of maximum likelihood classification for single particle electron cryo-microscopy that is based on the FREALIGN software. Particle alignment parameters are determined by maximizing a joint likelihood that can include hierarchical priors, while classification is performed by expectation maximization of a marginal likelihood. We test the FREALIGN implementation using a simulated dataset containing computer-generated projection images of three different 70S ribosome structures, as well as a publicly available dataset of 70S ribosomes. The results show that the mixed strategy of the new FREALIGN algorithm yields performance on par with other maximum likelihood implementations, while remaining computationally efficient.

KEYWORDS:

Classification; Electron microscopy; Maximum likelihood; Protein structure; Single particle

PMID:
23872434
PMCID:
PMC3824613
DOI:
10.1016/j.jsb.2013.07.005
[Indexed for MEDLINE]
Free PMC Article

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