Finding the right fit: chiseling structures out of cryo-electron microscopy maps

Cryo-electron microscopy is a central tool for studying the architecture of macromolecular complexes at subnanometer resolution. Interpretation of an electron microscopy map requires its computational integration with data about the structure's components from all available sources, notably atomic models. Selecting a protocol for EM density-guided integrative structural modeling depends on the resolution and quality of the EM map as well as the available complimentary datasets. Here, we review rigid, flexible, and de novo integrative fitting into EM maps and provide guidelines and considerations for the design of modeling experiments. Finally, we discuss efforts towards establishing unified criteria for map and model assessment and validation.