The field of cryo electron microscopy (cryo-EM) has seen dramatic advances in the past several years, with a rapidly growing number of near atomic resolution structures being published. This ‘resolution-revolution’ is a result of breakthroughs in detectors’ technology and computational methods. The highest resolution structures achieved by cryo-EM are of ridged single conformation proteins. However, the most important contribution of cryo-EM to our understanding of the molecular architecture of life, is its ability to determine structures in conformationally heterogeneous samples. While sorting out several conformations in a sample is already common in cryo-EM experiments, the ability to relate the different conformations to biochemical states and reaction coordinates is still under development. This talk will review how structures are determined in cryo-EM experiments and the ongoing computational and experimental directions for quantitative analysis of conformationally heterogeneous systems.
