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Sample Heterogeneity in Single Particle Imaging Using X-ray Lasers
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.ORCID iD: 0000-0002-0021-4354
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and Condensed Matter Physics.ORCID iD: 0000-0001-7328-0400
School of Science, RMIT University, Melbourne, Australia .
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(English)Manuscript (preprint) (Other academic)
Keywords [en]
X-ray free-electron laser, XFEL, Coherent diffractive imaging, CDI, Molecular dynamics, Single particle imaging, X-ray diffraction, Sample heterogeneity, Noise
National Category
Biophysics
Identifiers
URN: urn:nbn:se:uu:diva-382437OAI: oai:DiVA.org:uu-382437DiVA, id: diva2:1306907
Funder
Swedish Research CouncilThe Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Available from: 2019-04-25 Created: 2019-04-25 Last updated: 2019-04-28
In thesis
1. Simulations of Biomolecular Fragmentation and Diffraction with Ultrafast X-ray Lasers
Open this publication in new window or tab >>Simulations of Biomolecular Fragmentation and Diffraction with Ultrafast X-ray Lasers
2019 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Studies of biomolecules have recently seen substantial developments. New X-ray lasers allow for high-resolution imaging of protein crystals too small for conventional X-ray crystallography. Even structures of single particles have been determined at lower resolutions with these new sources. The secret lies in the ultrashort high-intensity pulses, which allow for diffraction and retrieval of structural information before the sample gets fragmented. However, the attainable resolution is still limited, in particular when imaging non-crystalline samples, making further advancements highly desired. In this thesis, some of the resolution-limiting obstacles facing single particle imaging (SPI) of proteins are studied in silico.

As the X-ray pulse interacts with injected single molecules, their spatial orientation is generally unknown. Recovering the orientation is essential to the structure determination process, and currently nontrivial. Molecular dynamics simulations show that the Coulomb explosion due to intense X-ray ionization could provide information pertaining to the original orientation. Used in conjunction with current methods, this would lead to an enhanced three-dimensional reconstruction of the protein.

Radiation damage and sample heterogeneity constitute considerable sources of noise in SPI. Pulse durations are presently not brief enough to circumvent damage, causing the sample to deteriorate during imaging, and the accuracy of the averaged diffraction pattern is impaired by structural variations. The extent of these effects were studied by molecular dynamics. Our findings suggest that radiation damage in terms of ionization and atomic displacement promotes a gating mechanism, benefiting imaging with longer pulses. Because of this, sample heterogeneity poses a greater challenge and efforts should be made to minimize its impact.

X-ray lasers generate pulses with a stochastic temporal distribution of photons, affecting the achievable resolution on a  pulse-to-pulse basis. Plasma simulations were performed to investigate how these fluctuations influence the damage dynamics and the diffraction signal. The results reveal that structural information is particularly well-preserved if the temporal distribution is skewed such that most photons are concentrated at the beginning.

While many obstacles remain, the prospect of atomic-resolution SPI is drawing ever closer. This thesis is but one of the stepping stones necessary to get us there. Once we do, the possibilities are limitless.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2019. p. 84
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1815
Keywords
X-ray free-electron laser, X-ray imaging, Single particle imaging, Computer simulation, Radiation damage, Molecular dynamics, Diffraction theory, Coulomb explosion, Sample heterogeneity, Diffractive noise, XFEL, SPI
National Category
Biophysics
Research subject
Physics with specialization in Biophysics
Identifiers
urn:nbn:se:uu:diva-382441 (URN)978-91-513-0669-8 (ISBN)
Public defence
2019-06-14, Häggsalen, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 10:15 (English)
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Supervisors
Funder
Swedish Research Council
Available from: 2019-05-23 Created: 2019-04-28 Last updated: 2019-06-18

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Östlin, ChristoferTimneanu, NicusorCaleman, C

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