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Updated: Feb 7, 2026

Subnanometer-resolution Structural Determination of Hemagglutinin from Cryo-electron Tomography of Influenza Viruses
Published on: November 7, 2025
IsoNet2 determines cellular structures at submolecular resolution without averaging
Z Hong Zhou1,2, Yun-Tao Liu1,2, Hongcheng Fan1,2,3
1Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles (UCLA), Los Angeles, CA 90095, USA.
None:
We introduce IsoNet2, an end-to-end self-supervised deep-learning method that directly reconstructs high-quality 3D densities from cryogenic electron tomograms. A unified network simultaneously performs denoising, contrast transfer function correction, and missing-wedge restoration, achieving ~20 Å resolution without averaging. A feature-rich GUI enables rapid, dataset-specific fine-tuning for end-users. IsoNet2 resolves domain organization in HIV capsid proteins, tRNA occupancy in individual ribosomes, and in situ architectures of mitochondrial respiration-related complexes, enabling atomic-level interpretation of cellular environments.
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