Abstract
Single-particle cryo-electron microscopy (cryo-EM) reconstructs the three-dimensional (3D) structure of biomolecules from a large set of 2D projection images with random and unknown orientations. A crucial step in the single-particle cryo-EM pipeline is 3D refinement, which resolves a highresolution 3D structure from an initial approximate volume by refining the estimation of the orientation of each projection. In this work, we propose a new approach that refines the projection angles on the continuum. We formulate the optimization problem over the density map and the orientations jointly. The density map is updated using the efficient alternating-direction method of multipliers, while the orientations are updated through a semicoordinate- wise gradient descent for which we provide an explicit derivation of the gradient. Our method eliminates the requirement for a fine discretization of the orientation space and does away with the classical but computationally expensive templatematching step. Numerical results demonstrate the feasibility and performance of our approach compared to several baselines.
Highlights
S INGLE-PARTICLE cryo-electron microscopy aims at obtaining the three-dimensional (3D) atomic structures of biological macromolecules such as proteins or viruses
It can be clearly seen that the results of our method (Figure 3-(d)) closely resemble the reconstructed map resulting from perfect knowledge of the latent variables
This shows the ability of our method to appropriately refine the density map and the latent variables
Summary
S INGLE-PARTICLE cryo-electron microscopy (cryo-EM) aims at obtaining the three-dimensional (3D) atomic structures of biological macromolecules such as proteins or viruses. Replicates of a molecule of interest, in unknown orientations, are first imaged at cryogenic temperatures. From those 2D projections (Figure 1 left), one reconstructs the 3D density map of the molecule (Figure 1 right), a computational process named “single-particle analysis” (SPA). Manuscript received August 14, 2019; revised February 23, 2020; accepted March 18, 2020. Date of publication April 1, 2020; date of current version May 5, 2020. The associate editor coordinating the review of this manuscript and approving it for publication was Dr Emanuele Salerno. The associate editor coordinating the review of this manuscript and approving it for publication was Dr Emanuele Salerno. (Corresponding author: Mona Zehni.)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
