Cryo-Electron Microscopy (cryo-EM) is an imaging technology that is revolutionizing structural biology. Cryo-electron microscopes produce many very noisy two-dimensional projection images of individual frozen molecules; unlike related methods, such as computed tomography (CT), the viewing direction of each particle image is unknown. The unknown directions and extreme noise make the determination of the structure of molecules challenging. While other methods for structure determination, such as x-ray crystallography and NMR, measure ensembles of molecules, cryo-electron microscopes produce images of individual particles. Therefore, cryo-EM could potentially be used to study mixtures of conformations of molecules. We will discuss a range of recent methods for analyzing the geometry of molecular conformations using cryo-EM data.
