The determinant factors for model resolutions obtained using CryoEM method

TL;DR

This paper develops a theoretical framework and simulations to identify key factors influencing CryoEM model resolution, highlighting the roles of image quantity, quality, molecular motion, and defocus levels.

Contribution

It introduces an analytical formula that quantifies how measurement quality, image number, molecular motion, and defocus affect CryoEM resolution.

Findings

Number of images and measurement quality dominate resolution.

Thermal motion significantly impacts resolution.

Defocus levels also affect the achievable resolution.

Abstract

The CryoEM single particle imaging method has recently received broad attention in the field of structural biology for determining the structures of biological molecules. The structures can be resolved to near-atomic resolutions after rending a large number of CryoEM images measuring molecules in different orientations. However, the factors for model resolution need to be further explored. Here, we provide a theoretical framework in conjunction with numerical simulations to gauge the influence of several key factors that are determinant in model resolution. We found that the number of measured projection images and the quality of each measurement (quantified using average signal-noise-ratio) can be combined to a single factor, which is dominant to the constructed model resolution. Furthermore, the intrinsic thermal motion of the molecules and the defocus levels of the electron microscope both have significant effects on the model resolution. These effects can be quantitatively summarized using an analytical formula that provides a theoretical guideline on structure resolutions for given experimental measurements.