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

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.