Algorithmic and Artificial Intelligence Methods for Protein Bioinformatics

Chapter 12

Computational Methods in CryoElectron Microscopy 3D Structure Reconstruction

FA ZHANG, XIAOHUA WAN, and ZHIYONG LIU

12.1 Introduction

Electron cryomicroscopy (cryoEM) is a rapidly emerging tool in structural biology for three-dimensional (3D) structure determination of macromolecular complexes. Single-particle cryoEM allows structural elucidation of macromolecular assemblies at subnanometer resolution [1, 2], and, in some cases, at atomic resolution [3]. Electron cryotomography (ET) allows structural studies of complex speciments at near-molecular resolution as well as visualization of macromolecular complexes in their native cellular context [4]. The integrative combination of these cryoEM modalities with other high-resolution approaches, such as X-ray crystallography or nuclear magnetic resonance (NMR), is expected to provide a comprehensive description of the cellular function in molecular detail [5].

In ET, a series of projection images where structural features from different layers of the 3D structure of the specimen are first superposed along the direction of the electron beam. In general, those images are obtained by tilting the specimen around tilt axes [6]. The 3D structure of the sample can then be derived from those projection images, by means of tomographic reconstruction algorithms [7]. Because of physical limitations of microscopes, the angular tilt range is limited and, as a result, tomographic tilt series have a wedge of missing data corresponding to ...