Cross-Validation of Data Compatibility Between Small Angle X-ray Scattering and Cryo-Electron Microscopy

Cryo-electron microscopy (EM) and small angle X-ray scattering (SAXS) are two different data acquisition modalities often used to glean information about the structure of large biomolecular complexes in their native states. A SAXS experiment is generally considered fast and easy but unveils the structure at very low resolution, whereas a cryo-EM experiment needs more extensive preparation and postacquisition computation to yield a three-dimensional (3D) density map at higher resolution. In certain applications, we may need to verify whether the data acquired in the SAXS and cryo-EM experiments correspond to the same structure (e.g., before reconstructing the 3D density map in EM). In this article, a simple and fast method is proposed to verify the compatibility of the SAXS and EM experimental data. The method is based on averaging the two-dimensional correlation of EM images and the Abel transform of the SAXS data. Orientational preferences are known to exist in cryo-EM experiments, and we also consider these effects on our method. The results are verified on simulations of conformational states of large biomolecular complexes.