Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics

Structure. 2008 May;16(5):673-83. doi: 10.1016/j.str.2008.03.005.


A novel method to flexibly fit atomic structures into electron microscopy (EM) maps using molecular dynamics simulations is presented. The simulations incorporate the EM data as an external potential added to the molecular dynamics force field, allowing all internal features present in the EM map to be used in the fitting process, while the model remains fully flexible and stereochemically correct. The molecular dynamics flexible fitting (MDFF) method is validated for available crystal structures of protein and RNA in different conformations; measures to assess and monitor the fitting process are introduced. The MDFF method is then used to obtain high-resolution structures of the E. coli ribosome in different functional states imaged by cryo-EM.

Publication types

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

MeSH terms

  • Aldehyde Oxidoreductases / chemistry
  • Computer Simulation*
  • Cryoelectron Microscopy
  • Crystallography, X-Ray
  • Escherichia coli / chemistry
  • Microscopy, Electron*
  • Models, Molecular
  • Molecular Conformation*
  • Multienzyme Complexes / chemistry
  • Nucleic Acid Conformation
  • Protein Conformation
  • RNA / chemistry
  • RNA, Bacterial / chemistry
  • RNA, Ribosomal, 16S / chemistry
  • RNA, Ribosomal, 16S / genetics
  • RNA, Transfer / chemistry
  • Reproducibility of Results
  • Ribosomes / chemistry*
  • Ribosomes / ultrastructure


  • Multienzyme Complexes
  • RNA, Bacterial
  • RNA, Ribosomal, 16S
  • RNA
  • RNA, Transfer
  • Aldehyde Oxidoreductases
  • carbon monoxide dehydrogenase