RECONSTRUCTING CONTINUOUS DISTRIBUTIONS OF 3D PROTEIN STRUCTURE FROM CRYO-EM IMAGES

Ellen D. Zhong, Tristan Bepler, Joseph H. Davis, Bonnie Berger

Research output: Contribution to conferencePaperpeer-review

26 Scopus citations

Abstract

Cryo-electron microscopy (cryo-EM) is a powerful technique for determining the structure of proteins and other macromolecular complexes at near-atomic resolution. In single particle cryo-EM, the central problem is to reconstruct the 3D structure of a macromolecule from 104-7 noisy and randomly oriented 2D projection images. However, the imaged protein complexes may exhibit structural variability, which complicates reconstruction and is typically addressed using discrete clustering approaches that fail to capture the full range of protein dynamics. Here, we introduce a novel method for cryo-EM reconstruction that extends naturally to modeling continuous generative factors of structural heterogeneity. This method encodes structures in Fourier space using coordinate-based deep neural networks, and trains these networks from unlabeled 2D cryo-EM images by combining exact inference over image orientation with variational inference for structural heterogeneity. We demonstrate that the proposed method, termed cryoDRGN, can perform ab initio reconstruction of 3D protein complexes from simulated and real 2D cryo-EM image data. To our knowledge, cryoDRGN is the first neural network-based approach for cryo-EM reconstruction and the first end-to-end method for directly reconstructing continuous ensembles of protein structures from cryo-EM images.

Original languageEnglish (US)
StatePublished - 2020
Externally publishedYes
Event8th International Conference on Learning Representations, ICLR 2020 - Addis Ababa, Ethiopia
Duration: Apr 30 2020 → …

Conference

Conference8th International Conference on Learning Representations, ICLR 2020
Country/TerritoryEthiopia
CityAddis Ababa
Period4/30/20 → …

All Science Journal Classification (ASJC) codes

  • Education
  • Linguistics and Language
  • Language and Linguistics
  • Computer Science Applications

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