Cryo-Electron Microscopy Modeling by the Molecular Dynamics Flexible Fitting Method

The increasing power and popularity of cryo‐electron microscopy (cryo‐EM) in structural biology brought about the development of so‐called hybrid methods, which permit the interpretation of cryo‐EM density maps beyond their nominal resolution in terms of atomic models. The Cryo‐EM Modeling Challenge 2010 is the first community effort to bring together developers of hybrid methods as well as cryo‐EM experimentalists. Participating in the challenge, the molecular dynamics flexible fitting (MDFF) method was applied to a number of cryo‐EM density maps. The results are described here with special emphasis on the use of symmetry‐based restraints to improve the quality of atomic models derived from density maps of symmetric complexes; on a comparison of the stereochemical quality of atomic models resulting from different hybrid methods; and on application of MDFF to electron crystallography data. © 2012 Wiley Periodicals, Inc. Biopolymers 97: 678–686, 2012.