Microcrystal electron diffraction (MicroED) is transforming the visualization of molecules from nanocrystals, rendering their three-dimensional atomic structures from previously unamenable samples. Peptidic structures determined by MicroED include naturally occurring peptides, synthetic protein fragments and peptide-based natural products. However, as a diffraction method, MicroED is beholden to the phase problem, and its de novo determination of structures remains a challenge. ARCIMBOLDO, an automated, fragment-based approach to structure determination. It eliminates the need for atomic resolution, instead enforcing stereochemical constraints through libraries of small model fragments, and discerning congruent motifs in solution space to ensure validation. This approach expands the reach of MicroED to presently inaccessible peptidic structures including segments of human amyloids, and yeast and mammalian prions, and portends a more general phasing solution while limiting model bias for a wider set of chemical structures.

中文翻译：

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MicroED 基于片段的肽纳米晶体从头开始定相

微晶电子衍射 (MicroED) 正在改变纳米晶体分子的可视化，从以前难以处理的样品中呈现它们的三维原子结构。MicroED 确定的肽结构包括天然存在的肽、合成蛋白质片段和基于肽的天然产物。然而，作为一种衍射方法，MicroED 受制于相位问题，它的de novo结构的确定仍然是一个挑战。ARCIMBOLDO，一种自动化的、基于片段的结构测定方法。它消除了对原子分辨率的需求，而是通过小模型片段库强制执行立体化学约束，并在解决方案空间中辨别全等基序以确保验证。这种方法将 MicroED 的范围扩展到目前无法访问的肽结构，包括人类淀粉样蛋白片段、酵母和哺乳动物朊病毒，并预示着更通用的定相解决方案，同时限制更广泛的化学结构集的模型偏差。