This is where you can find highlights of scientific papers published by the people of ESS. We will regularly be adding to this list, so do come back to learn more.
Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/16
In March 2020, the Deuteration and Macromolecular Crystallization (DEMAX) groups at the ESS issued a special call for proposals related to Covid-19 research. One of the projects has led to a larger collaboration between DEMAX, Frank Kozielski (University College London), and Wolfgang Knecht (Lund Protein Production Platform, LP3, at Lund University) and now the FragMAX platform of the MAX IV laboratory. The project is to find small molecule inhibitors that can block the SARS CoV-2 replication machinery. Non-structural protein 10 (nsp10) is a conserved stimulator of two enzymes crucial for viral replication, nsp14 and nsp16, exhibiting exoribonuclease and methlytransferase activities. Interfering with RNA proofreading or RNA cap formation represents intervention strategies that can be exploited to inhibit viral replication. Fragment-based screening using nano differential scanning fluorometry, x-ray crystallography and hit confirmation by microscale thermophoresis was carried out to identify ligands and measure their binding affinities to SARS-CoV-2 nsp10. Four fragments were identified that were found to bind to two distinct binding sites on nsp10: one can be modelled to where it would be located in the nsp14-nsp10 interface (Figure 1) and the other to the protein-protein interace of the nsp16-nsp10 complex. These fragments now serve as starting points for the development of more potent analogues using fragment growing techniques and structure-based drug design. This research used unique capabilities found at FragMAX and the BioMAX beamline, accessing a fragment library and making use of prioritized access to the BioMAX beamline, all during the ongoing pandemic
Cite: Kozielski F. et al. Identification of fragments binding to SARS-CoV-2 nsp10 reveals ligand-binding sites in conserved interfaces between nsp10 and nsp14/16. RSC Chemical Biology, 2021, doi:10.1039/D1CB00135C
ESS Contact: Zoë Fisher; LP3 Contact: Wolfgang Knecht; UCL Contact: Frank Kozielski; FragMAX Contact: Tobias Krojer
Stripping mechanisms and remediation for H- beams
The H- ion is often used for the accumulation of high-intensity proton populations in storage rings. This is done by stripping both its electrons (using either thin intercepting foils or laser stimulation) and bringing them into orbit with a circulating proton bunch. In doing so, higher intensities can be extracted from a ring than would be possible by simply injecting protons. The difficulty is reaching the ring: H- tends to have its weakly bound outer electron easily stripped away prior to the injection stage. This produces a neutral hydrogen atom, which follows a drift trajectory to ultimately collide and deposit most of its energy into external components, causing unwanted induced radioactivity. In this work, we summarize the theory governing the various types of stripping, from interaction with external fields or blackbody radiation, to collisions with adjacent H- ions. Simulated results are shown for practical test cases, where we demonstrate that the large majority of stripped hydrogen atoms deposit their energy into a final line-of-sight beam dump at the end of a linac or straight section, potentially relaxing the concerns for induced radioactivity of beam-line components.
Cite: Folsom B.T. et al. Stripping mechanisms and remediation for H- beams. Phys Rev Accel Beams 24, 074201, doi: 10.1103/PhysRevAccelBeams.24.074201
ESS Contact: Ben Folsom
Link: paper - https://link.aps.org/doi/10.1103/PhysRevAccelBeams.24.074201
Link: project video - https://www.youtube.com/watch?v=qAnvft0nAlg
Emergent magnetic behavior in the frustrated Yb3Ga5O12 garnet
Published 13 August 2021: Quintessential frustrated magnetic materials are those based on a triangular hyperkagome crystalline lattice and include the isostructural compounds Gd3Ga5O12 (GGG) and Yb3Ga5O12 (YGG). Our previous studies (Science 350, 6257 (2015)) uncovered a most unusual long range emergent director state in GGG derived from magnetic spins arranged on a ten-ion loop despite a disordered state at the local level. In this most recent work we show that the director state is also found in YGG, albeit correlated over a much reduced distance, revealing the ubiquity of this unusual state of matter. Neutron scattering experiments were performed on single crystal YGG, using the polarised diffuse scattering spectrometer, D7, at the ILL, the cold neutron scattering spectrometer, CNCS at the SNS and the thermal chopper spectrometer, IN4 at the ILL. An understanding of these novel states of matter in magnetic materials will result in technological breakthroughs beneficial to our spintronic society.
PHD students: R.Edberg (KTH), L: Sandberg (KU-ESS) and I.M. Bakke (Oslo University-ESS), supervised by Pascale Deen, Senior Scientist for Spectroscopy at ESS, Pascale Deen, and Adjunct Associate Professor, Niels Bohr Institute , University of Copenhagen.
Cite: Sandberg, L. Ø. et al. Emergent behavior in the frustrated Yb3Ga5O12 garnet. Phys. Rev. B. 104, 064425, doi:10.1103/PhysRevB.104.064425 (2021).
ESS Contact: Pascale Deen