Cryogenic electron-microscopy (cryo-EM) is an imaging technique able to recover the 3D structures of proteins at near-atomic resolution. A unique characteristic of cryo-EM is the possibility of recovering the structure of flexible proteins in different conformations from a single electron microscopy image dataset (called the heterogeneity problem). After an overview of the standard cryo-EM computational pipeline, I will discuss approaches to heterogeneity analysis. My focus will be on covering the state of the art and stating open problems.
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