1. Identifying Conformational States of Macromolecules by Eigen-Analysis of Resampled Cryo-EM Images
- Author
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Pawel A. Penczek, Marek Kimmel, and Christian M. T. Spahn
- Subjects
Models, Molecular ,Peptide Elongation Factor Tu ,Biology ,Article ,Reduction (complexity) ,Set (abstract data type) ,03 medical and health sciences ,Imaging, Three-Dimensional ,Bacterial Proteins ,RNA, Transfer ,Structural Biology ,Protein Interaction Domains and Motifs ,Protein Structure, Quaternary ,Projection (set theory) ,Molecular Biology ,030304 developmental biology ,Complex data type ,Analysis of Variance ,Principal Component Analysis ,0303 health sciences ,Thermus thermophilus ,Cryoelectron Microscopy ,030302 biochemistry & molecular biology ,Sample (graphics) ,Hypergeometric distribution ,Crystallography ,Principal component analysis ,Ribosome Subunits, Large ,Biological system ,Algorithms ,Curse of dimensionality - Abstract
SummaryWe present the codimensional principal component analysis (PCA), a novel and straightforward method for resolving sample heterogeneity within a set of cryo-EM 2D projection images of macromolecular assemblies. The method employs PCA of resampled 3D structures computed using subsets of 2D data obtained with a novel hypergeometric sampling scheme. PCA provides us with a small subset of dominating “eigenvolumes” of the system, whose reprojections are compared with experimental projection data to yield their factorial coordinates constructed in a common framework of the 3D space of the macromolecule. Codimensional PCA is unique in the dramatic reduction of dimensionality of the problem, which facilitates rapid determination of both the plausible number of conformers in the sample and their 3D structures. We applied the codimensional PCA to a complex data set of Thermus thermophilus 70S ribosome, and we identified four major conformational states and visualized high mobility of the stalk base region.
- Published
- 2011
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