While other methods for structure determination, such as x-ray crystallography and NMR, measure ensembles of molecules, cryo-electron microscopes (cryo-EM) produce images of individual particles. Therefore, cryo-EM could be used to study mixtures of conformations of molecules. Indeed, algorithms for analyzing a small number of distinct conformations have been very successful. We will discuss the different approaches emerging in recent years for the analysis of more complicated conformational heterogeneity and some of the difficulties that arise.
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