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10 mai 2019: 1 événement

  • Département Biochimie, Biophysique et Biologie Structurale

    Vendredi 10 mai 11:00-12:30 - Slavica Jonic - IMPMC - UMR 7590, Sorbonne Université/CNRS/MNHN, Paris

    Cryo-EM image analysis methods to study biomolecular conformational variability

    Résumé : Cryo electron microscopy (cryo-EM) has become comparable to X-ray crystallography with regards to the obtainable resolution of structures of biomolecular complexes, which are now increasingly determined at near-atomic resolution. To achieve such high resolutions, the classical approach is to collect a large number of cryo-EM images of complexes (particles) at random (unknown) orientations within a thin layer of vitreous ice, then, perform 2D and 3D classifications into an initially set number of classes and, finally, remove all those particles that do not contribute to the highest-resolution class averages (keep only particles with the most consistent views and conformations). Such “selection” of particles may obscure the information on a possibly larger conformational variability. More precisely, some conformational states may be thrown away blindly instead of being clearly elucidated while the characterization of different coexisting conformations may be essential for understanding how the complexes function and develop new drugs. Many classification-based image analysis methods exist and allow studying conformational changes assuming countable numbers of possible states (referred to as discrete-state methods) and the development of non-classification-based methods (referred to as continuous-state methods) is in progress. The latter methods assume uncountable numbers of states and aim at visualizing the full distribution of states. In this talk, I will review these different methods and describe in more detail the continuous-state method based on combining image analysis and normal mode analysis that has been developed in my lab.

    Lieu : Salle 102f - Bâtiment 14, Campus de Gif-sur-Yvette

    En savoir plus : Département Biochimie, Biophysique et Biologie Structurale