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BioMed Research International
Volume 2017, Article ID 1032432, 23 pages
Review Article

Structural Study of Heterogeneous Biological Samples by Cryoelectron Microscopy and Image Processing

Institute of Structural and Molecular Biology, University College London and Birkbeck, Malet Street, London WC1E 7HX, UK

Correspondence should be addressed to E. V. Orlova;

Received 15 September 2016; Accepted 23 November 2016; Published 15 January 2017

Academic Editor: Javier Vargas

Copyright © 2017 H. E. White et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


In living organisms, biological macromolecules are intrinsically flexible and naturally exist in multiple conformations. Modern electron microscopy, especially at liquid nitrogen temperatures (cryo-EM), is able to visualise biocomplexes in nearly native conditions and in multiple conformational states. The advances made during the last decade in electronic technology and software development have led to the revelation of structural variations in complexes and also improved the resolution of EM structures. Nowadays, structural studies based on single particle analysis (SPA) suggests several approaches for the separation of different conformational states and therefore disclosure of the mechanisms for functioning of complexes. The task of resolving different states requires the examination of large datasets, sophisticated programs, and significant computing power. Some methods are based on analysis of two-dimensional images, while others are based on three-dimensional studies. In this review, we describe the basic principles implemented in the various techniques that are currently used in the analysis of structural conformations and provide some examples of successful applications of these methods in structural studies of biologically significant complexes.