Coherent diffractive imaging of proteins and viral capsids: simulating MS SPIDOC

Area of Science:

• Biophysics
• Structural Biology
• Analytical Chemistry

Background:

• Single particle imaging at X-ray Free-Electron Lasers (XFELs) requires efficient sample delivery systems.
• Current methods face challenges in handling diverse biological samples (proteins to megadalton particles) and orienting them for imaging.

Purpose of the Study:

• To present the simulation package for the MS SPIDOC (Mass Spectrometry based Single Particle Isolation and Delivery Of Complex) system.
• To demonstrate the capability of MS SPIDOC for structural analysis of biological macromolecules using XFELs.

Main Methods:

• Developed a simulation package for front-to-end ion trajectory analysis.
• Utilized a quadrant lens for steering ion beams and ensuring spatial overlap with X-rays.
• Performed coherent diffractive imaging simulations and experiments on norovirus capsids using European XFEL parameters.

Main Results:

• Simulations confirmed the efficacy of the quadrant lens in ion beam steering.
• Demonstrated low-resolution diffractive imaging (q < 0.3 nm⁻¹) of T=1 and T=3 norovirus capsids using only a few X-ray pulses.
• Showed that MS SPIDOC can distinguish between different capsid symmetries, enabling the study of low-abundance species.

Conclusions:

• MS SPIDOC is a versatile sample delivery system adaptable to various XFEL beamlines.
• The system facilitates structural determination of biological particles, including distinguishing between different symmetries, with high efficiency.
• MS SPIDOC holds promise for probing low-abundance biological species in complex samples.