CryoDRGN2: Ab initio neural reconstruction of 3D protein structures from real cryo-EM images

Ellen D. Zhong, Adam Lerer, Joseph H. Davis, Bonnie Berger

Research output: Chapter in Book/Report/Conference proceedingConference contribution

5 Scopus citations

Abstract

Protein structure determination from cryo-EM data requires reconstructing a 3D volume (or distribution of volumes) from many noisy and randomly oriented 2D projection images. While the standard homogeneous reconstruction task aims to recover a single static structure, recently-proposed neural and non-neural methods can reconstruct distributions of structures, thereby enabling the study of protein complexes that possess intrinsic structural or conformational heterogeneity. These heterogeneous reconstruction methods, however, require fixed image poses, which are typically estimated from an upstream homogeneous reconstruction and are not guaranteed to be accurate under highly heterogeneous conditions. In this work we describe cryoDRGN2, an ab initio reconstruction algorithm, which can jointly estimate image poses and learn a neural model of a distribution of 3D structures on real heterogeneous cryo-EM data. To achieve this, we adapt search algorithms from the traditional cryo-EM literature, and describe the optimizations and design choices required to make such a search procedure computationally tractable in the neural model setting. We show that cryoDRGN2 is robust to the high noise levels of real cryo-EM images, trains faster than earlier neural methods, and achieves state-of-the-art performance on real cryo-EM datasets.

Original languageEnglish (US)
Title of host publicationProceedings - 2021 IEEE/CVF International Conference on Computer Vision, ICCV 2021
PublisherInstitute of Electrical and Electronics Engineers Inc.
Pages4046-4055
Number of pages10
ISBN (Electronic)9781665428125
DOIs
StatePublished - 2021
Externally publishedYes
Event18th IEEE/CVF International Conference on Computer Vision, ICCV 2021 - Virtual, Online, Canada
Duration: Oct 11 2021Oct 17 2021

Publication series

NameProceedings of the IEEE International Conference on Computer Vision
ISSN (Print)1550-5499

Conference

Conference18th IEEE/CVF International Conference on Computer Vision, ICCV 2021
Country/TerritoryCanada
CityVirtual, Online
Period10/11/2110/17/21

All Science Journal Classification (ASJC) codes

  • Software
  • Computer Vision and Pattern Recognition

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