Single particle imaging at atomic resolution is perhaps one of the most desired goals for ultrafast X-ray science with X-ray free-electron lasers. Such a capability would create great opportunity within the biological sciences, as high-resolution structural information of biosamples that may not crystallize is essential for many research areas therein. In this paper, we report on a comprehensive computational study of diffraction image formation during single particle imaging of a macromolecule, containing over one hundred thousand non-hydrogen atoms. For this study, we use a dedicated simulation framework, SIMEX, available at the European XFEL facility. Our results demonstrate the full feasibility of computational single-particle imaging studies for biological samples of realistic size. This finding is important as it shows that the SIMEX platform can be used for simulations to inform relevant single-particle-imaging experiments and help to establish optimal parameters for these experiments. This will enable more focused and more efficient single-particle-imaging experiments at XFEL facilities, making the best use of the resource-intensive XFEL operation.

原子分辨率的单粒子成像可能是使用 X 射线自由电子激光器的超快 X 射线科学最理想的目标之一。这种能力将在生物科学领域创造巨大的机会，因为可能不会结晶的生物样本的高分辨率结构信息对于其中的许多研究领域至关重要。在本文中，我们报告了对包含超过十万个非氢原子的大分子进行单粒子成像期间衍射图像形成的综合计算研究。在本研究中，我们使用欧洲 XFEL 设施提供的专用模拟框架 SIMEX。我们的结果证明了对真实尺寸的生物样本进行计算单粒子成像研究的完全可行性。这一发现很重要，因为它表明 SIMEX 平台可用于模拟，为相关的单粒子成像实验提供信息，并帮助为这些实验建立最佳参数。这将使 XFEL 设施的单粒子成像实验更加集中、更加高效，从而充分利用资源密集型 XFEL 操作。