title: Flexible fitting of atomic structures into electron microscopy maps using molecular dynamics.
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.
authors.affiliation: Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
authors.forename: Leonardo G
authors.initials: LG
authors.lastname: Trabuco
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Villa
authors.forename: Kakoli
authors.initials: K
authors.lastname: Mitra
authors.forename: Joachim
authors.initials: J
authors.lastname: Frank
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000737:chemistry; D003198:Computer Simulation; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000737:chemistry; D008854:Microscopy, Electron; D008958:Models, Molecular; D008968:Molecular Conformation; D009097:Multienzyme Complexes / Q000737:chemistry; D009690:Nucleic Acid Conformation; D011487:Protein Conformation; D012313:RNA / Q000737:chemistry; D012329:RNA, Bacterial / Q000737:chemistry; D012336:RNA, Ribosomal, 16S / Q000737:chemistry / Q000235:genetics; D012343:RNA, Transfer / Q000737:chemistry; D015203:Reproducibility of Results; D012270:Ribosomes / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D009097:Multienzyme Complexes; D012329:RNA, Bacterial; D012336:RNA, Ribosomal, 16S; D012313:RNA; D012343:RNA, Transfer; D000445:Aldehyde Oxidoreductases; C019823:carbon monoxide dehydrogenase