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Simulations of radiation damage as a function of the temporal pulse profile in femtosecond X-ray protein crystallography
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. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular biophysics.ORCID iD: 0000-0001-7328-0400
Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
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2015 (English)In: Journal of Synchrotron Radiation, ISSN 0909-0495, E-ISSN 1600-5775, Vol. 22, no 2, 256-266 p.Article in journal (Refereed) Published
Abstract [en]

Serial femtosecond X-ray crystallography of protein nanocrystals using ultrashort and intense pulses from an X-ray free-electron laser has proved to be a successful method for structural determination. However, due to significant variations in diffraction pattern quality from pulse to pulse only a fraction of the collected frames can be used. Experimentally, the X-ray temporal pulse profile is not known and can vary with every shot. This simulation study describes how the pulse shape affects the damage dynamics, which ultimately affects the biological interpretation of electron density. The instantaneously detected signal varies during the pulse exposure due to the pulse properties, as well as the structural and electronic changes in the sample. Here ionization and atomic motion are simulated using a radiation transfer plasma code. Pulses with parameters typical for X-ray free-electron lasers are considered: pulse energies ranging from 10$\sp 4$ to 10$\sp 7$Jcm$\sp $-$2$ with photon energies from 2 to 12keV, up to 100fs long. Radiation damage in the form of sample heating that will lead to a loss of crystalline periodicity and changes in scattering factor due to electronic reconfigurations of ionized atoms are considered here. The simulations show differences in the dynamics of the radiation damage processes for different temporal pulse profiles and intensities, where ionization or atomic motion could be predominant. The different dynamics influence the recorded diffracted signal in any given resolution and will affect the subsequent structure determination.

Place, publisher, year, edition, pages
2015. Vol. 22, no 2, 256-266 p.
Keyword [en]
X-ray free-electron laser, serial femtosecond crystallography, radiation damage, plasma simulations
National Category
Atom and Molecular Physics and Optics
Identifiers
URN: urn:nbn:se:uu:diva-245210DOI: 10.1107/S1600577515002878ISI: 000350641100007OAI: oai:DiVA.org:uu-245210DiVA: diva2:790702
Available from: 2015-02-25 Created: 2015-02-25 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Femtosecond Dynamics in Water and Biological Materials with an X-Ray Laser
Open this publication in new window or tab >>Femtosecond Dynamics in Water and Biological Materials with an X-Ray Laser
2016 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Using high intensity ultrashort pulses from X-ray free electron lasers to investigate soft matter is a recent and successful development. The last decade has seen the development of new variant of protein crystallography with femtosecond dynamics, and single particle imaging with atomic resolution is on the horizon. The work presented here is part of the effort to explain what processes influence the capability to achieve high resolution information in these techniques. Non-local thermal equilibrium plasma continuum modelling is used to predict signal changes as a function of pulse duration, shape and energy. It is found that ionization is the main contributor to radiation damage in certain photon energy and intensity ranges, and diffusion depending on heating is dominant in other scenarios. In femtosecond protein crystallography, self-gating of Bragg diffraction is predicted to quench the signal from the latest parts of an X-ray pulse. At high intensities ionization is dominant and the last part of the pulse will contain less information at low resolution. At lower intensities, displacement will dominate and high resolution information will be gated first. Temporal pulse shape is also an important factor. The difference between pulse shapes is most prominent at low photon energy in the form of a general increase or decrease in signal, but the resolution dependance is most prominent at high energies. When investigating the X-ray scattering from water a simple diffusion model can be replaced by a molecular dynamics simulation, which predicts structural changes in water on femtosecond timescales. Experiments performed at LCLS are presented that supports the simulation results on structural changes that occur in the solvent during the exposure.

Place, publisher, year, edition, pages
Uppsala universitet, 2016
National Category
Biophysics Atom and Molecular Physics and Optics
Research subject
Physics with specialization in Biophysics
Identifiers
urn:nbn:se:uu:diva-294553 (URN)
Presentation
2016-06-14, 80121, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, 15:19 (English)
Opponent
Supervisors
Available from: 2016-05-27 Created: 2016-05-24 Last updated: 2016-05-27Bibliographically approved
2. Advances in Biomolecular Imaging with X-ray Free-Electron Lasers
Open this publication in new window or tab >>Advances in Biomolecular Imaging with X-ray Free-Electron Lasers
2017 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Utilizing X-rays to solve molecular structures has proven to be an immensely powerful and im- portant scientific technique. The invention of X-ray crystallography has allowed for countless breakthroughs in chemistry, biology and material science and remains the number one method used for structural determination today. Of particular interest is the structures of biomolecules, such as proteins, due to their medical relevance. Unfortunately, the need for crystals of sufficient size constitutes the biggest drawback to this approach. This is troubling since many of the im- portant biomolecules, in particular membrane proteins, have proven to be difficult or sometimes even impossible to crystalize. When limited to a small nanocrystal or even a single particle, con- ventional crystallography is no longer adequate to probe the structure at high enough resolution. Recent developments, most notably the introduction of X-ray free-electron lasers (XFELs), have opened up new possibilities for circumventing these limitations. The high intensities and ultra- short pulse lengths provided by XFELs allows for diffractive imaging of smaller crystals through Serial Femtosecond Crystallography (SFX) and can even be extended to single molecules, Single Particle Imaging (SPI). These methods are still in their infancies, and much research and refine- ment is needed before they can be properly established.

The current work covers fundamental studies of X-ray interaction with biomatter carried out to aid and improve upon SFX and SPI. Three papers based on computer simulation studies are presented, related to mainly two central aspects faced when imaging molecules with XFELs. Pa- per I explores a novel approach using explosion mapping to facilitate spatial orientation of single particles, which is necessary to reconstruct the three dimensional structure from two dimensional diffraction patterns. Paper II concerns radiation damage of the sample in SFX experiments using a plasma model and studies the impact of different pulse profiles on these processes. Lastly, pa- per III outlines the details of an online database available to researchers worldwide that contains simulated data on damage development in samples exposed to an XFEL pulse.

In the first study, molecular dynamics was adopted to map the XFEL-induced Coulomb explo- sions in SPI for biomolecules. Four proteins were investigated, each with three different levels of hydration, and it was found that explosion patterns for both carbon and sulfur ions are re- producible for all twelve systems. However, water bound to the protein surface seems to have a shielding effect on carbons, causing their trajectories to be favored toward the exposed parts of the sample. This complicates the adoption for orientation determination as the water content would have to be known. Sulfurs, on the other hand, showed no signs of water dependence and consistently produced similar explosion patterns regardless of hydration level. We speculate that this is because of their higher mass and ionization cross section and conclude that mapping of heavier ions could provide valuable information for spatial orientation.

In the second study, radiation damage in terms of ionization and atomic displacement within a nanometer-sized crystal illuminated by an XFEL pulse was explored with a non-local thermody- namic equilibrium plasma code. Different temporal distributions of the same number of photons was employed to assess its impact of damage dynamics. The results show that the pulse profile is substantially important. A front-loaded pulse is more beneficial for imaging purposes since the bulk of the photons encounters an undamaged sample. If the majority of photons instead arrive late, early photons will already have initiated the crystal decay causing further contribution to the diffraction pattern to be degraded.

In the third study, the free-electron laser damage simulation database (FreeDam) was estab- lished. It presents simulated time-resolved data for average ionization, ion and electron temper- atures and atomic displacement for various materials and XFEL parameters. Simulations were carried out using the same code as in paper II, and the data is freely available online.

This thesis is aimed to provide one of the stepping stones toward atomic resolution imaging of nanocrystals and single particles with free-electron lasers. If realized, these techniques could well turn out to be one of the greatest scientific achievements of the 21th century.

Place, publisher, year, edition, pages
Uppsala University, 2017
Keyword
XFEL, serial femtosecond x-ray crystallography, single particle imaging, radiation damage, GROMACS, Cretin, computer simulation
National Category
Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:uu:diva-329500 (URN)
Presentation
2017-10-13, Å2001, Ångströmlaboratoriet, Lägerhyddsvägen 1, Uppsala, Sweden, 10:15 (Swedish)
Supervisors
Available from: 2017-09-18 Created: 2017-09-17 Last updated: 2017-09-18Bibliographically approved
3. Ultrafast Structural and Electron Dynamics in Soft Matter Exposed to Intense X-ray Pulses
Open this publication in new window or tab >>Ultrafast Structural and Electron Dynamics in Soft Matter Exposed to Intense X-ray Pulses
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Investigations of soft matter using ultrashort high intensity pulses have been made possible through the advent of X-ray free-electrons lasers. The last decade has seen the development of a new type of protein crystallography where femtosecond dynamics can be studied, and single particle imaging with atomic resolution is on the horizon. The pulses are so intense that any sample quickly turns into a plasma. This thesis studies the ultrafast transition from soft matter to warm dense matter, and the implications for structural determination of proteins.                   

We use non-thermal plasma simulations to predict ultrafast structural and electron dynamics. Changes in atomic form factors due to the electronic state, and displacement as a function of temperature, are used to predict Bragg signal intensity in protein nanocrystals. The damage processes started by the pulse will gate the diffracted signal within the pulse duration, suggesting that long pulses are useful to study protein structure. This illustrates diffraction-before-destruction in crystallography.

The effect from a varying temporal photon distribution within a pulse is also investigated. A well-defined initial front determines the quality of the diffracted signal. At lower intensities, the temporal shape of the X-ray pulse will affect the overall signal strength; at high intensities the signal level will be strongly dependent on the resolution.

Water is routinely used to deliver biological samples into the X-ray beam. Structural dynamics in water exposed to intense X-rays were investigated with simulations and experiments. Using pulses of different duration, we found that non-thermal heating will affect the water structure on a time scale longer than 25 fs but shorter than 75 fs. Modeling suggests that a loss of long-range coordination of the solvation shells accounts for the observed decrease in scattering signal.

The feasibility of using X-ray emission from plasma as an indicator for hits in serial diffraction experiments is studied. Specific line emission from sulfur at high X-ray energies is suitable for distinguishing spectral features from proteins, compared to emission from delivery liquids. We find that plasma emission continues long after the femtosecond pulse has ended, suggesting that spectrum-during-destruction could reveal information complementary to diffraction.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. 78 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1651-6214 ; 1592
Keyword
X-ray free-electron laser; Serial Femtosecond Crystallography; Radiation Damage; Plasma Simulations; Ultrafast Lasers; X-ray Imaging; Diffraction Theory; Ultrafast Phenomena; Hit Detection; Plasma Emission Spectra; Serial Femtosecond Crystallography; Protein Structure; Protein Crystallography; Metalloprotein; Non-thermal Heating; Water; Ferredoxin; NLTE Simulation; XFEL; FEL; SFX
National Category
Biophysics
Research subject
Physics with specialization in Biophysics
Identifiers
urn:nbn:se:uu:diva-331936 (URN)978-91-513-0134-1 (ISBN)
Public defence
2017-12-15, Polhemssalen, Lägerhyddsvägen 1, Uppsala, 09:15 (English)
Opponent
Supervisors
Funder
Swedish Foundation for Strategic Research , ICA10-0090Swedish Research Council, 2013-3940The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)
Available from: 2017-11-22 Created: 2017-10-25 Last updated: 2017-11-22

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Jönsson, H. OlofTimneanu, NicusorÖstlin, ChristoferCaleman, Carl

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