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Publications (10 of 111) Show all publications
Brodmerkel, M. N., De Santis, E., Uetrecht, C., Caleman, C. & Marklund, E. (2024). Collision induced unfolding and molecular dynamics simulations of norovirus capsid dimers reveal strain-specific stability profiles. Physical Chemistry, Chemical Physics - PCCP
Open this publication in new window or tab >>Collision induced unfolding and molecular dynamics simulations of norovirus capsid dimers reveal strain-specific stability profiles
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2024 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084Article in journal (Refereed) Published
Abstract [en]

Collision induced unfolding is method used with ion mobility mass spectrometry to examine protein structures and their stability. Such experiments yield information about higher order protein structures, yet are unable to provide details about the underlying processes. That information can however be provided using molecular dynamics simulations. Here, we investigate the collision induced unfolding of norovirus capsid dimers from the Norwalk and Kawasaki strains by employing molecular dynamics simulations over a range of temperatures, representing different levels of activation. The dimers have highly similar structures, but the activation reveals differences in the dynamics that arises in response to the activation.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2024
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-500271 (URN)10.1039/D3CP06344E (DOI)
Funder
Swedish Research Council, 2021-05988Swedish Research Council, 2020-04825Swedish Research Council, 2018-00740Swedish National Infrastructure for Computing (SNIC), 2022-22-854Swedish National Infrastructure for Computing (SNIC), 2022-22-925Swedish National Infrastructure for Computing (SNIC), 2022-22-947Swedish National Infrastructure for Computing (SNIC), 2022-5-415Swedish National Infrastructure for Computing (SNIC), 2022-23-57EU, Horizon 2020, 801406
Available from: 2023-04-13 Created: 2023-04-13 Last updated: 2024-04-11Bibliographically approved
Svensson, P., Schwob, L., Grånäs, O., Unger, I., Björneholm, O., Timneanu, N., . . . Berholts, M. (2024). Heavy element incorporation in nitroimidazole radiosensitizers: molecular-level insights into fragmentation dynamics. Physical Chemistry, Chemical Physics - PCCP, 26(2), 770-779
Open this publication in new window or tab >>Heavy element incorporation in nitroimidazole radiosensitizers: molecular-level insights into fragmentation dynamics
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2024 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 26, no 2, p. 770-779Article in journal (Refereed) Published
Abstract [en]

The present study investigates the photofragmentation behavior of iodine-enhanced nitroimidazole-based radiosensitizer model compounds in their protonated form using near-edge X-ray absorption mass spectrometry and quantum mechanical calculations. These molecules possess dual functionality: improved photoabsorption capabilities and the ability to generate species that are relevant to cancer sensitization upon photofragmentation. Four samples were investigated by scanning the generated fragments in the energy regions around C 1s, N 1s, O 1s, and I 3d-edges with a particular focus on NO2+ production. The experimental summed ion yield spectra are explained using the theoretical near-edge X-ray absorption fine structure spectrum based on density functional theory. Born-Oppenheimer-based molecular dynamics simulations were performed to investigate the fragmentation processes.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2024
National Category
Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:uu:diva-522697 (URN)10.1039/d3cp03800a (DOI)001090175100001 ()37888897 (PubMedID)
Funder
Swedish Research Council, 2019-03935Swedish Research Council, 2017-05128Swedish Research Council, 2018-00740Swedish Foundation for Strategic ResearchSwedish National Infrastructure for Computing (SNIC), 2022/1-36Swedish National Infrastructure for Computing (SNIC), 2022/22-597
Available from: 2024-02-08 Created: 2024-02-08 Last updated: 2024-02-08Bibliographically approved
Kierspel, T., Kadek, A., Barran, P., Bellina, B., Bijedic N, A., Brodmerkel, M. N., . . . Uetrecht, C. (2023). Coherent diffractive imaging of proteins and viral capsids: simulating MS SPIDOC. Analytical and Bioanalytical Chemistry, 415(18 SI), 4209-4220
Open this publication in new window or tab >>Coherent diffractive imaging of proteins and viral capsids: simulating MS SPIDOC
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2023 (English)In: Analytical and Bioanalytical Chemistry, ISSN 1618-2642, E-ISSN 1618-2650, Vol. 415, no 18 SI, p. 4209-4220Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
SPI, X-ray, Native MS, Protein complex structure, Viral particles, Simulation, Modeling
National Category
Biophysics
Identifiers
urn:nbn:se:uu:diva-500359 (URN)10.1007/s00216-023-04658-y (DOI)000963181300001 ()37014373 (PubMedID)
Funder
Swedish Research Council, 2018-00740Swedish Research Council, 2020-04825EU, Horizon 2020, 801406
Available from: 2023-04-14 Created: 2023-04-14 Last updated: 2024-01-26Bibliographically approved
Cardoch, S., Trost, F., Scott, H. A., Chapman, H. N., Caleman, C. & Timneanu, N. (2023). Decreasing ultrafast x-ray pulse durations with saturable absorption and resonant transitions. Physical review. E, 107(1), Article ID 015205.
Open this publication in new window or tab >>Decreasing ultrafast x-ray pulse durations with saturable absorption and resonant transitions
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2023 (English)In: Physical review. E, ISSN 2470-0045, E-ISSN 2470-0053, Vol. 107, no 1, article id 015205Article in journal (Refereed) Published
Abstract [en]

Saturable absorption is a nonlinear effect where a material's ability to absorb light is frustrated due to a high influx of photons and the creation of electron vacancies. Experimentally induced saturable absorption in copper revealed a reduction in the temporal duration of transmitted x-ray laser pulses, but a detailed account of changes in opacity and emergence of resonances is still missing. In this computational work, we employ nonlocal thermodynamic equilibrium plasma simulations to study the interaction of femtosecond x rays and copper. Following the onset of frustrated absorption, we find that a K–M resonant transition occurring at highly charged states turns copper opaque again. The changes in absorption generate a transient transparent window responsible for the shortened transmission signal. We also propose using fluorescence induced by the incident beam as an alternative source to achieve shorter x-ray pulses. Intense femtosecond x rays are valuable to probe the structure and dynamics of biological samples or to reach extreme states of matter. Shortened pulses could be relevant for emerging imaging techniques.

Place, publisher, year, edition, pages
American Physical SocietyAmerican Physical Society (APS), 2023
National Category
Atom and Molecular Physics and Optics Fusion, Plasma and Space Physics
Identifiers
urn:nbn:se:uu:diva-495128 (URN)10.1103/physreve.107.015205 (DOI)000923229600007 ()
Funder
Swedish Research Council, 2019-03935Swedish Research Council, 2018-00740German Research Foundation (DFG), 390715994
Available from: 2023-01-24 Created: 2023-01-24 Last updated: 2024-01-15Bibliographically approved
Trost, F., Ayyer, K., Prasciolu, M., Fleckenstein, H., Barthelmess, M., Yefanov, O., . . . Chapman, H. (2023). Imaging via Correlation of X-Ray Fluorescence Photons. Physical Review Letters, 130(17), Article ID 173201.
Open this publication in new window or tab >>Imaging via Correlation of X-Ray Fluorescence Photons
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2023 (English)In: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 130, no 17, article id 173201Article in journal (Refereed) Published
Abstract [en]

We demonstrate that x-ray fluorescence emission, which cannot maintain a stationary interference pattern, can be used to obtain images of structures by recording photon-photon correlations in the manner of the stellar intensity interferometry of Hanbury Brown and Twiss. This is achieved utilizing femtosecondduration pulses of a hard x-ray free-electron laser to generate the emission in exposures comparable to the coherence time of the fluorescence. Iterative phasing of the photon correlation map generated a model-free real-space image of the structure of the emitters. Since fluorescence can dominate coherent scattering, this may enable imaging uncrystallised macromolecules.

Place, publisher, year, edition, pages
American Physical Society, 2023
National Category
Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:uu:diva-503245 (URN)10.1103/PhysRevLett.130.173201 (DOI)000979791600002 ()37172237 (PubMedID)
Funder
German Research Foundation (DFG), EXC 2056German Research Foundation (DFG), 390715994Swedish Research Council, 2018-00740Swedish Research Council, 2019-03935
Available from: 2023-06-14 Created: 2023-06-14 Last updated: 2023-06-14Bibliographically approved
Kim, S., Sattorov, M., Hong, D., Kang, H., Park, J., Lee, J. H., . . . Park, G.-S. (2023). Observing ice structure of micron-sized vapor-deposited ice with an x-ray free-electron laser. Structural Dynamics, 10(4), Article ID 044302.
Open this publication in new window or tab >>Observing ice structure of micron-sized vapor-deposited ice with an x-ray free-electron laser
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2023 (English)In: Structural Dynamics, E-ISSN 2329-7778, Vol. 10, no 4, article id 044302Article in journal (Refereed) Published
Abstract [en]

The direct observation of the structure of micrometer-sized vapor-deposited ice is performed at Pohang Accelerator Laboratory x-ray free electron laser (PAL-XFEL). The formation of micrometer-sized ice crystals and their structure is important in various fields, including atmospheric science, cryobiology, and astrophysics, but understanding the structure of micrometer-sized ice crystals remains challenging due to the lack of direct observation. Using intense x-ray diffraction from PAL-XFEL, we could observe the structure of micrometer-sized vapor-deposited ice below 150K with a thickness of 2-50 mu m grown in an ultrahigh vacuum chamber. The structure of the ice grown comprises cubic and hexagonal sequences that are randomly arranged to produce a stacking-disordered ice. We observed that ice with a high cubicity of more than 80% was transformed to partially oriented hexagonal ice when the thickness of the ice deposition grew beyond 5 mu m. This suggests that precise temperature control and clean deposition conditions allow mu m-thick ice films with high cubicity to be grown on hydrophilic Si3N4 membranes. The low influence of impurities could enable in situ diffraction experiments of ice nucleation and growth from interfacial layers to bulk ice.

Place, publisher, year, edition, pages
American Institute of Physics (AIP), 2023
National Category
Condensed Matter Physics
Identifiers
urn:nbn:se:uu:diva-510783 (URN)10.1063/4.0000185 (DOI)001045012300001 ()37577135 (PubMedID)
Funder
Swedish Research Council, 2017-05128Swedish Research Council, 2021-1st-XSS-025Göran Gustafsson Foundation for promotion of scientific research at Uppala University and Royal Institute of Technology, 1808
Available from: 2023-09-07 Created: 2023-09-07 Last updated: 2023-09-07Bibliographically approved
Gopakumar, G., Unger, I., Slavicek, P., Hergenhahn, U., Oehrwall, G., Malerz, S., . . . Björneholm, O. (2023). Radiation damage by extensive local water ionization from two-step electron-transfer-mediated decay of solvated ions. Nature Chemistry, 15(10), 1408-+
Open this publication in new window or tab >>Radiation damage by extensive local water ionization from two-step electron-transfer-mediated decay of solvated ions
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2023 (English)In: Nature Chemistry, ISSN 1755-4330, E-ISSN 1755-4349, Vol. 15, no 10, p. 1408-+Article in journal (Refereed) Published
Abstract [en]

Biomolecular radiation damage is largely mediated by radicals and low-energy electrons formed by water ionization rather than by direct ionization of biomolecules. It was speculated that such an extensive, localized water ionization can be caused by ultrafast processes following excitation by core-level ionization of hydrated metal ions. In this model, ions relax via a cascade of local Auger-Meitner and, importantly, non-local charge- and energy-transfer processes involving the water environment. Here, we experimentally and theoretically show that, for solvated paradigmatic intermediate-mass Al3+ ions, electronic relaxation involves two sequential solute-solvent electron transfer-mediated decay processes. The electron transfer-mediated decay steps correspond to sequential relaxation from Al5+ to Al3+ accompanied by formation of four ionized water molecules and two low-energy electrons. Such charge multiplication and the generated highly reactive species are expected to initiate cascades of radical reactions.

Place, publisher, year, edition, pages
Nature Publishing Group, 2023
National Category
Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-526069 (URN)10.1038/s41557-023-01302-1 (DOI)001188164500001 ()37620544 (PubMedID)
Available from: 2024-04-05 Created: 2024-04-05 Last updated: 2024-04-05Bibliographically approved
Brodmerkel, M. N., De Santis, E., Caleman, C. & Marklund, E. (2023). Rehydration Post-orientation: Investigating Field-Induced Structural Changes via Computational Rehydration. The Protein Journal, 42(3), 205-218
Open this publication in new window or tab >>Rehydration Post-orientation: Investigating Field-Induced Structural Changes via Computational Rehydration
2023 (English)In: The Protein Journal, ISSN 1572-3887, E-ISSN 1875-8355, Vol. 42, no 3, p. 205-218Article in journal (Refereed) Published
Abstract [en]

Proteins can be oriented in the gas phase using strong electric fields, which brings advantages for structure determination using X-ray free electron lasers. Both the vacuum conditions and the electric-field exposure risk damaging the protein structures. Here, we employ molecular dynamics simulations to rehydrate and relax vacuum and electric-field exposed proteins in aqueous solution, which simulates a refinement of structure models derived from oriented gas-phase proteins. We find that the impact of the strong electric fields on the protein structures is of minor importance after rehydration, compared to that of vacuum exposure and ionization in electrospraying. The structures did not fully relax back to their native structure in solution on the simulated timescales of 200 ns, but they recover several features, including native-like intra-protein contacts, which suggests that the structures remain in a state from which the fully native structure is accessible. Our fndings imply that the electric fields used in native mass spectrometry are well below a destructive level, and suggest that structures inferred from X-ray difraction from gas-phase proteins are relevant for solution and in vivo conditions, at least after in silico rehydration.

Place, publisher, year, edition, pages
Springer Nature, 2023
Keywords
Molecular dynamics simulation, Protein hydration, Electric dipole, Protein structure, Structural biology, X-rays
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-499999 (URN)10.1007/s10930-023-10110-y (DOI)000966256600001 ()37031302 (PubMedID)
Funder
Swedish Research Council, 2020-04825Swedish Research Council, 2018-00740Swedish Research Council, 2021-05988EU, Horizon 2020, 801406
Available from: 2023-04-10 Created: 2023-04-10 Last updated: 2023-08-15Bibliographically approved
Trost, F., Ayyer, K., Oberthuer, D., Yefanov, O., Bajt, S., Caleman, C., . . . Chapman, H. N. (2023). Speckle contrast of interfering fluorescence X-rays. Journal of Synchrotron Radiation, 30(1), 11-23
Open this publication in new window or tab >>Speckle contrast of interfering fluorescence X-rays
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2023 (English)In: Journal of Synchrotron Radiation, ISSN 0909-0495, E-ISSN 1600-5775, Vol. 30, no 1, p. 11-23Article in journal (Refereed) Published
Abstract [en]

With the development of X-ray free-electron lasers (XFELs), producing pulses of femtosecond durations comparable with the coherence times of X-ray fluorescence, it has become possible to observe intensity–intensity correlations due to the interference of emission from independent atoms. This has been used to compare durations of X-ray pulses and to measure the size of a focusedX-ray beam, for example. Here it is shown that it is also possible to observe the interference of fluorescence photons through the measurement of the speckle contrast of angle-resolved fluorescence patterns. Speckle contrast is often used as a measure of the degree of coherence of the incident beam or the fluctuations of the illuminated sample as determined from X-ray diffraction patterns formed by elastic scattering, rather than from fluorescence patterns as addressed here. Commonly used approaches to estimate speckle contrast were found to suffer when applied to XFEL-generated fluorescence patterns due to low photon counts and a significant variation of the excitation pulse energy from shot to shot. A new method to reliably estimate speckle contrast under such conditions, using a weighting scheme, is introduced. The method is demonstrated by comparing the speckle contrast of fluorescence observed with pulses of 3 fs to 15 fs duration.

Place, publisher, year, edition, pages
International Union Of CrystallographyInternational Union of Crystallography (IUCr), 2023
Keywords
speckle contrast estimation, X-ray fluorescence, incoherent diffraction imaging, XPCS
National Category
Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:uu:diva-495130 (URN)10.1107/s1600577522009997 (DOI)000908417600002 ()36601922 (PubMedID)
Funder
German Research Foundation (DFG), 390715994Swedish Research Council, 2019-03935Swedish Research Council, 2018-00740
Available from: 2023-01-24 Created: 2023-01-24 Last updated: 2024-01-15Bibliographically approved
Cardoch, S., Timneanu, N., Caleman, C. & Scheicher, R. H. (2022). Distinguishing between Similar Miniproteins with Single-Molecule Nanopore Sensing: A Computational Study. ACS Nanoscience Au, 2(2), 119-127
Open this publication in new window or tab >>Distinguishing between Similar Miniproteins with Single-Molecule Nanopore Sensing: A Computational Study
2022 (English)In: ACS Nanoscience Au, E-ISSN 2694-2496, Vol. 2, no 2, p. 119-127Article in journal (Refereed) Published
Abstract [en]

A nanopore is a tool in single-molecule sensing biotechnology that offers label-free identification with high throughput. Nanopores have been successfully applied to sequence DNA and show potential in the study of proteins. Nevertheless, the task remains challenging due to the large variability in size, charges, and folds of proteins. Miniproteins have a small number of residues, limited secondary structure, and stable tertiary structure, which can offer a systematic way to reduce complexity. In this computational work, we theoretically evaluated sensing two miniproteins found in the human body using a silicon nitride nanopore. We employed molecular dynamics methods to compute occupied-pore ionic current magnitudes and electronic structure calculations to obtain interaction strengths between pore wall and miniprotein. From the interaction strength, we derived dwell times using a mix of combinatorics and numerical solutions. This latter approach circumvents typical computational demands needed to simulate translocation events using molecular dynamics. We focused on two miniproteins potentially difficult to distinguish owing to their isotropic geometry, similar number of residues, and overall comparable structure. We found that the occupied-pore current magnitudes not to vary significantly, but their dwell times differ by 1 order of magnitude. Together, these results suggest a successful identification protocol for similar miniproteins.

Place, publisher, year, edition, pages
American Chemical Society (ACS), 2022
National Category
Condensed Matter Physics
Identifiers
urn:nbn:se:uu:diva-495139 (URN)10.1021/acsnanoscienceau.1c00022 (DOI)001027123700001 ()37101662 (PubMedID)
Funder
Swedish Research Council, 2017-04627Swedish Research Council, 2018-00740Swedish Research Council, 2019-03935
Available from: 2023-01-24 Created: 2023-01-24 Last updated: 2023-10-09Bibliographically approved
Projects
Structural and electronic rearrangement in bio-molecules induced by X-ray Free-electron Laser pulses [2013-03940_VR]; Uppsala UniversitySolving the orientation problem in Single Particle Imaging using XFEL [2018-00740_VR]; Uppsala University
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0003-2638-1940

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