FiXR: a framework to reconstruct fiber cross-sections from X-ray fiber diffraction experiments.

Area of Science:

• Biophysics
• Structural Biology
• Materials Science

Background:

• Small-angle X-ray scattering (SAXS) has enabled molecular conformation discovery for globular molecules.
• Existing SAXS methods are limited for analyzing large, periodic fibrillar assemblies due to their size and complex scattering profiles.

Purpose of the Study:

• To develop a novel approach for inferring the cross-sectional electron distribution of fibers from SAXS data.
• To advance the structural analysis of fibrillar assemblies, which are challenging for current molecular discovery tools.

Main Methods:

• Utilized SAXS measurements combined with diffraction theory to model fiber cross-sections.
• Employed a discrete electron density model with continuous support, allowing for non-binary distributions and incorporating constraints like non-negativity and smoothness.
• Tested the method with simulated SAXS data of amyloid β fibril models and experimental data from Tobacco mosaic virus.

Main Results:

• Successfully recovered the geometry and density of cross-sections for both simulated and experimental SAXS data.
• Validated the approach by analyzing SAXS data from various amyloid β fibril assemblies, achieving results consistent with cryo-electron microscopy (cryo-EM) findings.
• Demonstrated the method's capability to represent electron density beyond simple binary distributions.

Conclusions:

• The proposed SAXS-based method provides a robust framework for determining the cross-sectional structure of fibrillar assemblies.
• This technique offers a valuable alternative and complement to existing methods like cryo-EM for studying complex biological and material structures.
• Further research should explore the method's limitations and its integration with other experimental techniques for enhanced structural elucidation.