Macromolecular assembly structures by comparative modeling and electron microscopy

Methods Mol Biol. 2012:857:331-50. doi: 10.1007/978-1-61779-588-6_15.


Advances in electron microscopy allow for structure determination of large biological machines at increasingly higher resolutions. A key step in this process is fitting component structures into the electron microscopy-derived density map of their assembly. Comparative modeling can contribute by providing atomic models of the components, via fold assignment, sequence-structure alignment, model building, and model assessment. All four stages of comparative modeling can also benefit from consideration of the density map. In this chapter, we describe numerous types of modeling problems restrained by a density map and available protocols for finding solutions. In particular, we provide detailed instructions for density map-guided modeling using the Integrative Modeling Platform (IMP), MODELLER, and UCSF Chimera.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Chaperonin 60 / chemistry
  • Escherichia coli / chemistry
  • Escherichia coli Proteins / chemistry
  • Macromolecular Substances / chemistry*
  • Microscopy, Electron / methods*
  • Models, Molecular*
  • Molecular Sequence Data
  • Protein Conformation
  • Proteins / chemistry*
  • Sequence Alignment / methods


  • Chaperonin 60
  • Escherichia coli Proteins
  • Macromolecular Substances
  • Proteins