Flexible Fitting of Atomic Structures into Electron Microscopy Maps Using Molecular Dynamics

• DOI: 10.1016/j.str.2008.03.005
• Publication Date: 2008-05-07T14:16:15Z
• Authors: Leonardo G. Trabuco; Elizabeth Villa; Kakoli Mitra; Joachim Frank; Klaus Schulten
• Keywords: Models, Molecular; 0301 basic medicine; 0303 health sciences; PROTEINS; Protein Conformation; Cryoelectron Microscopy; Molecular Conformation; Reproducibility of Results; Crystallography, X-Ray; Aldehyde Oxidoreductases; Microscopy, Electron; RNA, Bacterial; 03 medical and health sciences; RNA, Transfer; Structural Biology; Multienzyme Complexes; RNA, Ribosomal, 16S; Escherichia coli; Nucleic Acid Conformation; RNA; Computer Simulation; Molecular Biology; Ribosomes

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.