Molecular size dependence on achievable resolution from XFEL single-particle 3D reconstruction

Single-particle analysis using x-ray free-electron lasers (XFELs) is a novel method for obtaining structural information of samples in a state close to nature. In particular, it is suitable for observing the inner structure of large biomolecules by taking advantage of the high transmittance of x-rays. However, systematic studies on the resolution achievable for large molecules are lacking. In this study, the molecular size dependence of the resolution of a three-dimensional (3D) structure resulting from XFEL single-particle reconstruction is evaluated using synthetic data. Evidently, 3D structures of larger molecules can be restored with higher detail (defined relative to the molecular sizes) than smaller ones; however, reconstruction with high absolute resolution (defined in nm(-1)) is challenging. Our results provide useful information for the experimental design of 3D structure reconstruction using coherent x-ray diffraction patterns of single-particles.

Automated summary

Single-particle analysis using x-ray free-electron lasers is a novel method for obtaining structural information of samples. This study evaluates the resolution of three-dimensional structures obtained from XFEL single-particle reconstruction using synthetic data. It is found that larger molecules can be restored with higher detail relative to their size, but achieving high absolute resolution is challenging.