title: Continuous changes in structure mapped by manifold embedding of single-particle data in cryo-EM.
abstract: Cryo-electron microscopy, when combined with single-particle reconstruction, is a powerful method for studying macromolecular structure. Recent developments in detector technology have pushed the resolution into a range comparable to that of X-ray crystallography. However, cryo-EM is able to separate and thus recover the structure of each of several discrete structures present in the sample. For the more general case involving continuous structural changes, a novel technique employing manifold embedding has been recently demonstrated. Potentially, the entire work-cycle of a molecular machine may be observed as it passes through a continuum of states, and its free-energy landscape may be mapped out. This technique will be outlined and discussed in the context of its application to a large single-particle dataset of yeast ribosomes.
authors.affiliation: Howard Hughes Medical Institute, Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, United States; Department of Biological Sciences, Columbia University, New York, NY 10027, United States. Electronic address: jf2192@cumc.columbia.edu.
authors.forename: Joachim
authors.initials: J
authors.lastname: Frank
authors.affiliation: Department of Physics, University of Wisconsin Milwaukee, 3135 N. Maryland Ave, Milwaukee, WI 53211, United States. Electronic address: ourmazd@uwm.edu.
authors.forename: Abbas
authors.initials: A
authors.lastname: Ourmazd
mesh_terms: D020285:Cryoelectron Microscopy / Q000379:methods*; D005656:Fungal Proteins / Q000648:ultrastructure*; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D012270:Ribosomes / Q000648:ultrastructure*; D015003:Yeasts
chemical_list: D005656:Fungal Proteins
keywords: Classification; Heterogeneity; Machine learning; Molecular machines; Protein synthesis; Ribosome