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PMID: 18462672 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Structure (London, England : 1993) ·Vol. 16 ·No. 5 ·2008-05-00 ·Pages 673-83

Trabuco LG, Villa E, Mitra K, Frank J, Schulten K

Abstract

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.

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,genetics RNA, Transfer/chemistry Reproducibility of Results Ribosomes/chemistry,ultrastructure
Chemicals
Multienzyme Complexes RNA, Bacterial RNA, Ribosomal, 16S RNA RNA, Transfer Aldehyde Oxidoreductases carbon monoxide dehydrogenase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Trabuco Leonardo G
Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Villa Elizabeth
Mitra Kakoli
Frank Joachim
Schulten Klaus
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Article Info
Journal
Structure (London, England : 1993)
Abbr.
Structure
ISSN
0969-2126
DOI
10.1016/j.str.2008.03.005
Published
2008-05-00
Pages
673-83
Language
English
Region
United States
NLM ID
101087697
PMCID
PMC2430731
Subset
IM
Grants
NCRR NIH HHS · P41 RR005969 · United States
NCRR NIH HHS · P41-RR01219 · United States
NCRR NIH HHS · P41 RR001219 · United States
NIGMS NIH HHS · R01 GM055440 · United States
NIGMS NIH HHS · R37-GM29169 · United States
NCRR NIH HHS · P41 RR005969-18 · United States
NCRR NIH HHS · P41-RR05969 · United States
NIGMS NIH HHS · R01-GM55440 · United States
NIGMS NIH HHS · R37 GM029169 · United States
External Links
PubMed source DOI: 10.1016/j.str.2008.03.005 PMC Full Text View journal details
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