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# Cryogenic Electron Microscopy

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  1. bioRxiv

    CryoEM maps no longer just show a shape: cryoID2 pairs sequence and structure to pick PfA-M17 out of 166 proteins

    CryoEM can reconstruct a density map yet often cannot say which molecule the map contains, and matching hundreds or thousands of mass-spectrometry or genome-derived candidates by hand is a bottleneck. CryoID2 uses three 3D U-Nets to predict structure classes, key-atom positions and reduced residue or nucleotide types from the map, turns them into short sequence queries that rank candidates, then rigidly fits the candidates' PDB or AlphaFold models back into the density and ranks them by agreement. In a 166-protein mass-spectrometry pool it placed PF3D7_1446200/PfA-M17 first and selected PDB 4ZX8 as the best structural model; on the RNA side it ranked the Ca-raiA-containing interval fourth in a genome-derived non-coding pool, and structural evaluation then put PDB 9E73 first.

  2. arXiv

    Cryo-EM skips the density-map detour: EB-FM learns atomic-coordinate conformational distributions straight from 2D projections

    Standard cryo-EM pipelines first reconstruct a 3D density from 2D projections and only then fit an atomic model, so atomic-coordinate priors never reach the most under-determined stage. EB-FM trains a flow-matching prior inside a Monte Carlo stochastic-approximation expectation-maximization loop, repeatedly inverting the nonlinear imaging forward model during training, so no clean structures are needed for pretraining. On simulated cryo-EM data with known poses it recovers conformational distributions directly in atomic-coordinate space for four proteins, though predicted motion amplitudes stay below the molecular-dynamics ground truth.

  3. Ultra-cold microscopy reaches the lab: the liquid-helium STEM GAIA and the road to atomic-resolution cryogenic imaging

    This evidence bundle centres on a Nature news feature reporting that Bruker will ship GAIA, described as the first scanning transmission electron microscope to operate stably near absolute zero with liquid helium, to three laboratories in Canada, Germany and the United States, where it can image materials at about −266 °C (7 kelvin) for 30 hours or more, while tracing the earlier route: a 2025 US-reported TEM attachment reaching −253 °C (20 kelvin) with atomic-resolution imaging stable for more than ten hours, a condenZero liquid-helium attachment at around 4 kelvin for 24 hours that did not aim for atomic resolution, and Idrobo's 2021 comment on aberration correction combined with further instrument developments.

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