Ab initio reconstruction methods have revolutionized the capabilities of small‐angle X‐ray scattering (SAXS), allowing the data‐driven discovery of previously unknown molecular conformations, exploiting optimization heuristics and assumptions behind the composition of globular molecules. While these methods have been successful for the analysis of small particles, their impact on fibrillar assemblies has been more limited. The micrometre‐range size of these assemblies and the complex interaction of their periodicities in their scattering profiles indicate that the discovery of fibril structures from SAXS measurements requires novel approaches beyond extending existing tools for molecular discovery. In this work, it is proposed to use SAXS measurements, together with diffraction theory, to infer the electron distribution of the average cross‐section of a fiber. This cross‐section is modeled as a discrete electron density with continuous support, allowing representations beyond binary distributions. Additional constraints, such as non‐negativity or smoothness/connectedness, can also be added to the framework. The proposed approach is tested using simulated SAXS data from amyloid β fibril models and using measured data of Tobacco mosaic virus from SAXS experiments, recovering the geometry and density of the cross‐sections in all cases. The approach is further tested by analyzing SAXS data from different amyloid β fibril assemblies, with results that are in agreement with previously proposed models from cryo‐EM measurements. The limitations of the proposed method, together with an analysis of the robustness of the method and the combination with different experimental sources, are also discussed.

中文翻译：

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FiXR：从X射线纤维衍射实验重建纤维横截面的框架。

从头算重建方法彻底改变了小角度X射线散射（SAXS）的功能，允许以数据驱动的方式发现先前未知的分子构象，并利用优化启发法和球形分子组成背后的假设。尽管这些方法已成功用于分析小颗粒，但它们对原纤维组件的影响却更为有限。这些组件的微米范围大小以及它们在散射分布图中周期性的复杂相互作用表明，从SAXS测量中发现原纤维结构需要新颖的方法，而不仅仅是扩展现有的分子发现工具。在这项工作中，建议结合使用SAXS测量和衍射理论，推断出纤维平均截面的电子分布。该横截面建模为具有连续支撑的离散电子密度，从而可以表示超出二元分布的范围。还可以将其他约束（例如非负性或平滑性/连接性）添加到框架中。使用来自淀粉样蛋白β原纤维模型的模拟SAXS数据和来自SAXS实验的烟草花叶病毒的测量数据，对所提出的方法进行了测试，以在所有情况下恢复横截面的几何形状和密度。通过分析来自不同淀粉样β原纤维组件的SAXS数据，对该方法进行了进一步测试，其结果与先前从cryo-EM测量中提出的模型相符。所提出方法的局限性，