Biophysical Society Thematic Meeting | Trieste 2024

Emerging Theoretical Approaches to Complement Single-Particle Cryo-EM Wednesday Speaker Abstracts

ENABLING VISUAL PROTEOMICS BY HIGH-CONFIDENCE 3D TEMPLATE MATCHING Sergio Cruz-Leon 1 ; Tomáš Majtner 2 ; Patrick C Hoffmann 2 ; Jan Philipp Kreysing 2 ; Sebastian Kehl 3 ; Maarten W Tuijtel 2 ; Stefan L Schaefer 1 ; Katharina Geißler 2 ; Martin Beck 2 ; Beata Turonová 2 ; Gerhard Hummer 1 ; 1 Max Planck Institute of Biophysics, Department of Theoretical Biophysics, Frankfurt am Main, Germany 2 Max Planck Institute of Biophysics, Department of Molecular Sociology, Frankfurt am Main, Germany 3 Max Planck Computing and Data Facility, Garching, Germany By creating detailed 3D maps of the interior of cells, visual proteomics aims to understand the spatial interactions between macromolecular complexes in their native environment. Cryo electron tomography (CryoET) offers a powerful approach for imaging the interior of cells with fully preserved context. However, the complex and noisy nature of CryoET data hinders feature identification. In my talk, I will present our recent advances in high confidence 3D template matching (hcTM) for CryoET. hcTM enables automated, objective, and comprehensive detection of a wide range of cellular structures within crowded cells. The high-confidence nature of our approach opens doors to unexpected biological discoveries and the computational modelling of realistic subcellular systems. By enabling the reliable detection of individual complexes in different conformational states, we can establish robust connections between their functional state, spatial localization, cellular context, and even cell type and species. Our work sets the stage for analyzing individual molecular events inside living cells with defined statistical confidence.

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