# Cross-Modal Fusion Between Data in SAXS and Cryo-EM for Biomolecular Structure Determination

## TL;DR

This paper introduces a method that combines SAXS and cryo-EM data to improve biomolecular structure determination, especially in cases with limited projection directions, by leveraging the complementary strengths of both techniques.

## Contribution

It presents a novel approach for integrating SAXS with cryo-EM data to address anisotropy and coverage issues in biomolecular imaging.

## Key findings

- SAXS can fill in blind spots in cryo-EM data.
- Combined data improves structure resolution in challenging cases.
- Method enhances biomolecular structure determination accuracy.

## Abstract

Cryo-Electron Microscopy (cryo-EM) has become an extremely powerful method for resolving structural details of large biomolecular complexes. However, challenging problems in single-particle methods remain open because of (1) the low signal-to-noise ratio in EM; and (2) the potential anisotropy and lack of coverage of projection directions relative to the body-fixed coordinate system for some complexes. Whereas (1) is usually addressed by class averaging (and increasingly due to rapid advances in microscope and sensor technology), (2) is an artifact of the mechanics of interaction of biomolecular complexes and the vitrification process. In the absence of tilt series, (2) remains a problem, which is addressed here by supplementing EM data with Small-Angle X-Ray Scattering (SAXS). Whereas SAXS is of relatively low resolution and contains much lower information content than EM, we show that it is nevertheless possible to use SAXS to fill in blind spots in EM in difficult cases where the range of projection directions is limited.