Random Conical Tilt Reconstruction without Particle Picking in Cryo-electron Microscopy

TL;DR

This paper introduces a novel method for 3D molecular structure reconstruction in cryo-electron microscopy that bypasses particle picking by using autocorrelation analysis on micrographs collected at a single tilt angle.

Contribution

The proposed approach enables direct 3D reconstruction from micrographs without particle picking, simplifying the process and potentially lowering size limits in cryo-EM.

Findings

Successful reconstruction with simulated data

Effect of missing-cone region analyzed

Potential to reduce size limit for single particle cryo-EM

Abstract

We propose a method to reconstruct the 3-D molecular structure from micrographs collected at just one sample tilt angle in the random conical tilt scheme in cryo-electron microscopy. Our method uses autocorrelation analysis on the micrographs to estimate features of the molecule which are invariant under certain nuisance parameters such as the positions of molecular projections in the micrographs. This enables us to reconstruct the molecular structure directly from micrographs, completely circumventing the need for particle picking. We demonstrate reconstructions with simulated data and investigate the effect of the missing-cone region. These results show promise to reduce the size limit for single particle reconstruction in cryo-electron microscopy.