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

MS SPIDOC Consortium, Thomas Kierspel, Alan Kadek, Perdita Barran, Bruno Bellina, Adi Bijedic, Maxim N. Brodmerkel, Jan Commandeur, Carl Caleman, Tomislav Damjanović, Ibrahim Dawod, Emiliano De Santis, Alexandros Lekkas, Kristina Lorenzen, Luis López Morillo, Thomas Mandl, Erik G. Marklund, Dimitris Papanastasiou, Lennart A.I. Ramakers, Lutz SchweikhardFlorian Simke, Anna Sinelnikova, Athanasios Smyrnakis, Nicusor Timneanu, Charlotte Uetrecht

Research output: Contribution to journalArticlepeer-review


MS SPIDOC is a novel sample delivery system designed for single (isolated) particle imaging at X-ray Free-Electron Lasers that is adaptable towards most large-scale facility beamlines. Biological samples can range from small proteins to MDa particles. Following nano-electrospray ionization, ionic samples can be m/z-filtered and structurally separated before being oriented at the interaction zone. Here, we present the simulation package developed alongside this prototype. The first part describes how the front-to-end ion trajectory simulations have been conducted. Highlighted is a quadrant lens; a simple but efficient device that steers the ion beam within the vicinity of the strong DC orientation field in the interaction zone to ensure spatial overlap with the X-rays. The second part focuses on protein orientation and discusses its potential with respect to diffractive imaging methods. Last, coherent diffractive imaging of prototypical T = 1 and T = 3 norovirus capsids is shown. We use realistic experimental parameters from the SPB/SFX instrument at the European XFEL to demonstrate that low-resolution diffractive imaging data (q < 0.3 nm−1) can be collected with only a few X-ray pulses. Such low-resolution data are sufficient to distinguish between both symmetries of the capsids, allowing to probe low abundant species in a beam if MS SPIDOC is used as sample delivery.

Original languageEnglish
Pages (from-to)4209-4220
Number of pages12
JournalAnalytical and bioanalytical chemistry
Issue number18
Early online date4 Apr 2023
Publication statusPublished - 1 Jul 2023


  • Modeling
  • Native MS
  • Protein complex structure
  • Simulation
  • SPI
  • Viral particles
  • X-ray


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