A statistical approach to detect protein complexes at X-ray free electron laser facilities
Journal article, 2018
The Flash X-ray Imaging (FXI) technique, under development at X-ray free electron lasers (XFEL), aims to achieve structure determination based on diffraction from individual macromolecular complexes. We report an FXI study on the first protein complex-RNA polymerase II-ever injected at an XFEL. A successful 3D reconstruction requires a high number of observations of the sample in various orientations. The measured diffraction signal for many shots can be comparable to background. Here we present a robust and highly sensitive hit-identification method based on automated modeling of beamline background through photon statistics. It can operate at controlled false positive hit-rate of 3 x10(-5). We demonstrate its power in determining particle hits and validate our findings against an independent hit-identification approach based on ion time-of-flight spectra. We also validate the advantages of our method over simpler hit-identification schemes via tests on other samples and using computer simulations, showing a doubled hit-identification power.
Author
Alberto Pietrini
Uppsala University
Johan Bielecki
European XFEL
Uppsala University
Nicusor Timneanu
Uppsala University
Max F. Hantke
Uppsala University
University of Oxford
Jakob Andreasson
Uppsala University
Czech Academy of Sciences
Chalmers, Physics, Condensed Matter Physics
N. Duane Loh
National University of Singapore (NUS)
Daniel S. D. Larsson
Uppsala University
Sebastien Boutet
Stanford University
Janos Hajdu
Czech Academy of Sciences
Uppsala University
Filipe R. N. C. Maia
Uppsala University
Carl Nettelblad
Uppsala University
Communications Physics
23993650 (eISSN)
Vol. 1 92Subject Categories
Accelerator Physics and Instrumentation
Atom and Molecular Physics and Optics
Bioinformatics (Computational Biology)
DOI
10.1038/s42005-018-0092-6