Logo: to the web site of Uppsala University

uu.sePublications from Uppsala University
Change search
Link to record
Permanent link

Direct link
De Santis, Emiliano, PhDORCID iD iconorcid.org/0000-0001-5029-7429
Publications (10 of 12) 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
Show others...
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
Wollter, A., De Santis, E., Ekeberg, T., Marklund, E. G. & Caleman, C. (2024). Enhanced EMC-Advantages of partially known orientations in x-ray single particle imaging. Journal of Chemical Physics, 160(11), Article ID 114108.
Open this publication in new window or tab >>Enhanced EMC-Advantages of partially known orientations in x-ray single particle imaging
Show others...
2024 (English)In: Journal of Chemical Physics, ISSN 0021-9606, E-ISSN 1089-7690, Vol. 160, no 11, article id 114108Article in journal (Refereed) Published
Abstract [en]

Single particle imaging of proteins in the gas phase with x-ray free-electron lasers holds great potential to study fast protein dynamics, but is currently limited by weak and noisy data. A further challenge is to discover the proteins' orientation as each protein is randomly oriented when exposed to x-rays. Algorithms such as the expand, maximize, and compress (EMC) exist that can solve the orientation problem and reconstruct the three-dimensional diffraction intensity space, given sufficient measurements. If information about orientation were known, for example, by using an electric field to orient the particles, the reconstruction would benefit and potentially reach better results. We used simulated diffraction experiments to test how the reconstructions from EMC improve with particles' orientation to a preferred axis. Our reconstructions converged to correct maps of the three-dimensional diffraction space with fewer measurements if biased orientation information was considered. Even for a moderate bias, there was still significant improvement. Biased orientations also substantially improved the results in the case of missing central information, in particular in the case of small datasets. The effects were even more significant when adding a background with 50% the strength of the averaged diffraction signal photons to the diffraction patterns, sometimes reducing the data requirement for convergence by a factor of 10. This demonstrates the usefulness of having biased orientation information in single particle imaging experiments, even for a weaker bias than what was previously known. This could be a key component in overcoming the problems with background noise that currently plague these experiments.

Place, publisher, year, edition, pages
American Institute of Physics (AIP), 2024
National Category
Biophysics
Identifiers
urn:nbn:se:uu:diva-528478 (URN)10.1063/5.0188772 (DOI)001187986000015 ()38506290 (PubMedID)
Funder
EU, Horizon 2020, 801406EU, Horizon 2020, 101120312Swedish Research Council, 2020-04825Swedish Research Council, 2018-00740Swedish Foundation for Strategic Research, ITM17-0455Swedish Research Council, 2017-05336
Available from: 2024-05-23 Created: 2024-05-23 Last updated: 2024-05-23Bibliographically approved
Pihlava, L., Svensson, P., Kukk, E., Kooser, K., De Santis, E., Tonisoo, A., . . . Berholts, M. (2024). Shell-dependent photofragmentation dynamics of a heavy-atom-containing bifunctional nitroimidazole radiosensitizer. Physical Chemistry, Chemical Physics - PCCP, 26(11), 8879-8890
Open this publication in new window or tab >>Shell-dependent photofragmentation dynamics of a heavy-atom-containing bifunctional nitroimidazole radiosensitizer
Show others...
2024 (English)In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 26, no 11, p. 8879-8890Article in journal (Refereed) Published
Abstract [en]

Radiation therapy uses ionizing radiation to break chemical bonds in cancer cells, thereby causing DNA damage and leading to cell death. The therapeutic effectiveness can be further increased by making the tumor cells more sensitive to radiation. Here, we investigate the role of the initial halogen atom core hole on the photofragmentation dynamics of 2-bromo-5-iodo-4-nitroimidazole, a potential bifunctional radiosensitizer. Bromine and iodine atoms were included in the molecule to increase the photoionization cross-section of the radiosensitizer at higher photon energies. The fragmentation dynamics of the molecule was studied experimentally in the gas phase using photoelectron-photoion-photoion coincidence spectroscopy and computationally using Born-Oppenheimer molecular dynamics. We observed significant changes between shallow core (I 4d, Br 3d) and deep core (I 3d) ionization in fragment formation and their kinetic energies. Despite the fact, that the ions ejected after deep core ionization have higher kinetic energies, we show that in a cellular environment, the ion spread is not much larger, keeping the damage well-localized. A study on photodissociation dynamics of 2-bromo-5-iodo-nitroimidazole - a model radiosensitizer - using coincidence spectroscopy and computational methods.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2024
National Category
Atom and Molecular Physics and Optics Physical Chemistry
Identifiers
urn:nbn:se:uu:diva-528495 (URN)10.1039/d4cp00367e (DOI)001175892400001 ()38426309 (PubMedID)
Funder
Swedish Research Council, 2023-04346Swedish Research Council, 2018-00740
Available from: 2024-05-22 Created: 2024-05-22 Last updated: 2024-05-22Bibliographically 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
Show others...
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
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
Lindblad, R., Kjellsson, L., De Santis, E., Zamudio-Bayer, V., von Issendorff, B., Sorensen, S. L., . . . Couto, R. C. (2022). Experimental and theoretical near-edge x-ray-absorption fine-structure studies of NO+. Physical Review A: covering atomic, molecular, and optical physics and quantum information, 106(4), Article ID 042814.
Open this publication in new window or tab >>Experimental and theoretical near-edge x-ray-absorption fine-structure studies of NO+
Show others...
2022 (English)In: Physical Review A: covering atomic, molecular, and optical physics and quantum information, ISSN 2469-9926, E-ISSN 2469-9934, Vol. 106, no 4, article id 042814Article in journal (Refereed) Published
Abstract [en]

Experimental near-edge x-ray-absorption fine-structure (NEXAFS) spectra of the nitrosonium NO+ ion are presented and theoretically analyzed. While neutral NO has an open shell, the cation is a closed-shell species, which for NEXAFS leads to the simplicity of a closed-shell spectrum. Compared to neutral NO, the electrons in the cation experience a stronger Coulomb potential, which introduces a shift of the ionization potential towards higher energies, a depletion of intensity in a large interval above the pi* resonance, and a shift of the sigma* resonance from the continuum to below the ionization threshold. NEXAFS features at the nitrogen and oxygen K edges of NO+ are compared, as well as NEXAFS features at the nitrogen edges of the isoelectronic closed-shell species NO+, N2, and N2H+.

Place, publisher, year, edition, pages
American Physical Society, 2022
National Category
Atom and Molecular Physics and Optics
Research subject
Physics
Identifiers
urn:nbn:se:uu:diva-488287 (URN)10.1103/physreva.106.042814 (DOI)000879523600001 ()
Funder
Swedish Research Council, SNIC 2021/3-22Swedish Research Council, 637-2014-6929Swedish Research Council, 2014-04518EU, Horizon 2020, 730872
Available from: 2022-11-11 Created: 2022-11-11 Last updated: 2023-04-05Bibliographically approved
Nucara, A., Ripanti, F., Sennato, S., Nisini, G., De Santis, E., Sefat, M., . . . Carbone, M. (2022). Influence of Cortisol on the Fibril Formation Kinetics of A beta 42 Peptide: A Multi-Technical Approach. International Journal of Molecular Sciences, 23(11), Article ID 6007.
Open this publication in new window or tab >>Influence of Cortisol on the Fibril Formation Kinetics of A beta 42 Peptide: A Multi-Technical Approach
Show others...
2022 (English)In: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 23, no 11, article id 6007Article in journal (Refereed) Published
Abstract [en]

Amyloid-beta peptide (A beta) aggregates are known to be correlated with pathological neurodegenerative diseases. The fibril formation process of such peptides in solution is influenced by several factors, such as the ionic strength of the buffer, concentration, pH, and presence of other molecules, just to mention a few. In this paper, we report a detailed analysis of in vitro A beta 42 fibril formation in the presence of cortisol at different relative concentrations. The thioflavin T fluorescence assay allowed us to monitor the fibril formation kinetics, while a morphological characterization of the aggregates was obtained by atomic force microscopy. Moreover, infrared absorption spectroscopy was exploited to investigate the secondary structure changes along the fibril formation path. Molecular dynamics calculations allowed us to understand the intermolecular interactions with cortisol. The combined results demonstrated the influence of cortisol on the fibril formation process: indeed, at cortisol-A beta 42 concentration ratio (rho) close to 0.1 a faster organization of A beta 42 fragments into fibrils is promoted, while for rho = 1 the formation of fibrils is completely inhibited.

Place, publisher, year, edition, pages
MDPI AG, 2022
Keywords
A beta 42 peptide, fibril formation, ThT fluorescence, secondary structure, infrared spectroscopy, atomic force microscopy, molecular dynamics
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-478803 (URN)10.3390/ijms23116007 (DOI)000809177300001 ()35682687 (PubMedID)
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2022-06-27 Created: 2022-06-27 Last updated: 2022-06-27Bibliographically approved
De Santis, E., Minicozzi, V., Rossi, G., Stellato, F. & Morante, S. (2022). Is styrene competitive for dopamine receptor binding?. Biomolecular Concepts, 13(1), 200-206
Open this publication in new window or tab >>Is styrene competitive for dopamine receptor binding?
Show others...
2022 (English)In: Biomolecular Concepts, ISSN 1868-503X, Vol. 13, no 1, p. 200-206Article in journal (Refereed) Published
Abstract [en]

The potential role of styrene oxide in altering the dopaminergic pathway in the ear is investigated by means of molecular docking and molecular dynamics simulations. We estimate the binding affinity of both styrene oxide and dopamine to the dopaminergic receptor DrD2 by computing the free-energy difference, ∆G, between the configuration where the ligand is bound to the receptor and the situation in which it is “infinitely” far away from it. The results show that the styrene oxide has a somewhat lower affinity for binding with respect to dopamine, which, however, may not be enough to prevent exogenous high concentration styrene oxide to compete with endogenous dopamine for DrD2 binding.

Place, publisher, year, edition, pages
Walter de Gruyter, 2022
Keywords
umbrella sampling, dopamine, styrene oxide, binding affinity
National Category
Biophysics
Identifiers
urn:nbn:se:uu:diva-500358 (URN)10.1515/bmc-2022-0016 (DOI)
Available from: 2023-04-14 Created: 2023-04-14 Last updated: 2023-04-17Bibliographically approved
Brodmerkel, M. N., De Santis, E., Uetrecht, C., Caleman, C. & Marklund, E. (2022). Stability and conformational memory of electrosprayed and rehydrated bacteriophage MS2 virus coat proteins. Current Research in Structural Biology, 4, 338-348
Open this publication in new window or tab >>Stability and conformational memory of electrosprayed and rehydrated bacteriophage MS2 virus coat proteins
Show others...
2022 (English)In: Current Research in Structural Biology, E-ISSN 2665-928X, Vol. 4, p. 338-348Article in journal (Refereed) Published
Abstract [en]

Proteins are innately dynamic, which is important for their functions, but which also poses significant challenges when studying their structures. Gas-phase techniques can utilise separation and a range of sample manipulations to transcend some of the limitations of conventional techniques for structural biology in crystalline or solution phase, and isolate different states for separate interrogation. However, the transfer from solution to the gas phase risks affecting the structures, and it is unclear to what extent different conformations remain distinct in the gas phase, and if resolution in silico can recover the native conformations and their differences. Here, we use extensive molecular dynamics simulations to study the two distinct conformations of dimeric capsid protein of the MS2 bacteriophage. The protein undergoes notable restructuring of its peripheral parts in the gas phase, but subsequent simulation in solvent largely recovers the native structure. Our results suggest that despite some structural loss due to the experimental conditions, gas-phase structural biology techniques provide meaningful data that inform not only about the structures but also conformational dynamics of proteins.

Place, publisher, year, edition, pages
Elsevier, 2022
Keywords
Molecular dynamics simulations, Bacteriophage, Gas-phase structure, Protein structure, Solvation, Electrospray ionization
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:uu:diva-499621 (URN)10.1016/j.crstbi.2022.10.001 (DOI)36440379 (PubMedID)
Funder
Swedish Research Council, 2020-04825EU, Horizon 2020, 801406Swedish Research Council, 2021-05988
Available from: 2023-04-03 Created: 2023-04-03 Last updated: 2023-10-19Bibliographically approved
Dawod, I., Cardoch, S., André, T., De Santis, E., E, J., Mancuso, A. P., . . . Timneanu, N.MolDStruct: modelling the dynamics and structure of matter exposed to ultrafast X-ray lasers with hybrid collisional-radiative/molecular dynamics.
Open this publication in new window or tab >>MolDStruct: modelling the dynamics and structure of matter exposed to ultrafast X-ray lasers with hybrid collisional-radiative/molecular dynamics
Show others...
(English)Manuscript (preprint) (Other academic)
Abstract [en]

We describe a method to compute photon-matter interaction and atomic dynamics with X-ray lasers using a hybrid code based on classical molecular dynamics and collisional-radiative calculations. The forces between the atoms are dynamically computed based on changes to their electronic occupations and the free electron cloud created due to the irradiation of photons in the X-ray spectrum. The rapid transition from neutral solid matter to dense plasma phase allows the use of screened potentials, which reduces the number of non-bonded interactions required to compute. In combination with parallelization through domain decomposition, large-scale molecular dynamics and ionization induced by X-ray lasers can be followed. This method is applicable for large enough samples (solids, liquids, proteins, viruses, atomic clusters and crystals) that when exposed to an X-ray laser pulse turn into a plasma in the first few femtoseconds of the interaction. We show several examples of the applicability of the method and we quantify the sizes that the method is suitable for. For large systems, we investigate non-thermal heating and scattering of bulk water, which we compare to previous experiments. We simulate molecular dynamics of a protein crystal induced by an X-ray pump, X-ray probe scheme, and find good agreement of the damage dynamics with experiments. For single particle imaging, we simulate ultrafast dynamics of a methane cluster exposed to a femtosecond X-ray laser. In the context of coherent diffractive imaging we study the fragmentation as given by an X-ray pump X-ray probe setup to understand the evolution of radiation damage.

National Category
Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:uu:diva-519450 (URN)
Projects
In thesis
Funder
Swedish Research Council, 2018- 00740, 2019-03935
Available from: 2024-01-08 Created: 2024-01-08 Last updated: 2024-01-09
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-5029-7429

Search in DiVA

Show all publications