A fragment based method for modeling of protein segments into cryo-EM density maps

BMC Bioinformatics. 2017 Nov 13;18(1):475. doi: 10.1186/s12859-017-1904-5.


Background: Single-particle analysis of electron cryo-microscopy (cryo-EM) is a key technology for elucidation of macromolecular structures. Recent technical advances in hardware and software developments significantly enhanced the resolution of cryo-EM density maps and broadened the applicability and the circle of users. To facilitate modeling of macromolecules into cryo-EM density maps, fast and easy to use methods for modeling are now demanded.

Results: Here we investigated and benchmarked the suitability of a classical and well established fragment-based approach for modeling of segments into cryo-EM density maps (termed FragFit). FragFit uses a hierarchical strategy to select fragments from a pre-calculated set of billions of fragments derived from structures deposited in the Protein Data Bank, based on sequence similarly, fit of stem atoms and fit to a cryo-EM density map. The user only has to specify the sequence of the segment and the number of the N- and C-terminal stem-residues in the protein. Using a representative data set of protein structures, we show that protein segments can be accurately modeled into cryo-EM density maps of different resolution by FragFit. Prediction quality depends on segment length, the type of secondary structure of the segment and local quality of the map.

Conclusion: Fast and automated calculation of FragFit renders it applicable for implementation of interactive web-applications e.g. to model missing segments, flexible protein parts or hinge-regions into cryo-EM density maps.

Keywords: Cryo-EM; Flexible fitting; Fragment based modeling.

Publication types

  • Validation Study

MeSH terms

  • Cryoelectron Microscopy / methods*
  • Databases, Protein
  • Models, Molecular
  • Protein Structure, Secondary
  • Proteins / chemistry*
  • Software


  • Proteins