title: Iterative elastic 3D-to-2D alignment method using normal modes for studying structural dynamics of large macromolecular complexes.
abstract: This article presents a method to study large-scale conformational changes by combining electron microscopy (EM) single-particle image analysis and normal mode analysis (NMA). It is referred to as HEMNMA, which stands for hybrid electron microscopy normal mode analysis. NMA of a reference structure (atomic-resolution structure or EM volume) is used to predict possible motions that are then confronted with EM images within an automatic iterative elastic 3D-to-2D alignment procedure to identify actual motions in the imaged samples. HEMNMA can be used to extensively analyze the conformational changes and may be used in combination with classic discrete procedures. The identified conformations allow modeling of deformation pathways compatible with the experimental data. HEMNMA was tested with synthetic and experimental data sets of E. coli 70S ribosome, DNA polymerase Pol α and B subunit complex of the eukaryotic primosome, and tomato bushy stunt virus.
authors: IMPMC, Sorbonne Universités-CNRS UMR 7590, UPMC Paris 6, MNHN, IRD UMR 206, 4 Place Jussieu, 75005 Paris, France.
authors: Qiyu
authors: Q
authors: Jin
authors: Biocomputing Unit, Centro Nacional de Biotecnología-CSIC, Madrid 28049, Spain.
authors: Carlos Oscar S
authors: CO
authors: Sorzano
authors: Biocomputing Unit, Centro Nacional de Biotecnología-CSIC, Madrid 28049, Spain.
authors: José Miguel
authors: JM
authors: de la Rosa-Trevín
authors: Departamento de Informática, Universidad de Almería, Almería 04120, Spain.
authors: José Román
authors: JR
authors: Bilbao-Castro
authors: Centro de Investigaciones Biológicas, CSIC, Madrid 28040, Spain.
authors: Rafael
authors: R
authors: Núñez-Ramírez
authors: Centro de Investigaciones Biológicas, CSIC, Madrid 28040, Spain.
authors: Oscar
authors: O
authors: Llorca
authors: RIKEN, Advanced Institute for Computational Sciences, Kobe, Hyogo 650-0047, Japan.
authors: Florence
authors: F
authors: Tama
authors: IMPMC, Sorbonne Universités-CNRS UMR 7590, UPMC Paris 6, MNHN, IRD UMR 206, 4 Place Jussieu, 75005 Paris, France. Electronic address: slavica.jonic@impmc.upmc.fr.
authors: Slavica
authors: S
authors: Jonić
mesh_terms: D019295:Computational Biology / Q000379:methods*; D020285:Cryoelectron Microscopy / Q000379:methods; D004256:DNA Polymerase I / Q000737:chemistry; D019951:DNA Polymerase beta / Q000737:chemistry; D004926:Escherichia coli; D007091:Image Processing, Computer-Assisted; D046911:Macromolecular Substances / Q000737:chemistry*; D008854:Microscopy, Electron; D008958:Models, Molecular; D011487:Protein Conformation; D012270:Ribosomes / Q000737:chemistry
chemical_list: D046911:Macromolecular Substances; D004256:DNA Polymerase I; D019951:DNA Polymerase beta