Computational Methods for Interpretation of EM Maps at Subnanometer Resolution

Abstract

Abstract Driven by a remarkable number of technological advances in recent years, electron cryo‐microscopy (cryo‐EM) has played an increasingly important role in deciphering macromolecular structure and function. Today, cryo‐EM routinely achieves subnanometer resolutions, with current state‐of‐the‐art reconstructions approaching atomic resolutions. Though achieving high‐resolution density maps is still a challenging aspect of cryo‐EM, it is possible to isolate individual subunits, identify secondary structures elements and accurately fit atomic models in reconstructions of large macromolecular assemblies. Additionally, computational modelling and feature recognition tools are routinely employed to construct backbone and atomic models of entire assemblies directly from a density map. Together, these tools provide researchers with unprecedented insight into structure and function, revealing everything from subunit arrangements to complex sets of interactions in macromolecular assemblies. Key Concepts: Cryo‐EM is capable of imaging large macromolecular assemblies in order to understand their structure and function. Analysing macromolecular assemblies requires a variety of complex computational tools. In subnanometer resolution cryo‐EM density maps, it is possible to see individual protein subunits, as well as higher‐resolution structural features. It is now possible to construct backbone and atomic models directly from cryo‐EM density maps at near‐atomic resolutions.