Exploring Dynamic Nuclear Polarisation for Neutron Protein Crystallography

Lead Research Organisation: University of Leicester
Department Name: Molecular and Cell Biology


United States


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Ashkar R (2018) Neutron scattering in the biological sciences: progress and prospects. in Acta crystallographica. Section D, Structural biology

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Kwon H (2018) The rise of neutron cryo-crystallography. in Acta crystallographica. Section D, Structural biology

Description The application of DNP (a development that will mean it is possible to see hydrogen atoms in much smaller samples and more quickly than at present using neutron crystallography) is being developed at ONRL. The technique requires polarising a beam of neutrons and holding a protein sample at millikelvin temperatures to hold its electronic alignment. ONRL have invested several million dollars establishing the technology. Much of this work is still confidential. The access given to me and my discussions with the beam line scientists and the head of section has given me an appreciation of the difficulties involved and enables a realistic appraisal of how my research can both contribute to, and benefit from the ONRL program.
I invited the lead scientist on the project to contribute a chapter in a volume of Methods in Enzymology I edited, the url is given below
Exploitation Route If we can make DNP work, it will revolutionise neutron protein crystallography. The ability to use smaller crystals and to avoid deuterium exchange or perdueterated protein will vastly increase the scope of the technique. Where hydrogens have been seen using existing neutron crystallography, rather than being extrapolated from heavy atom positions, it has had a big impact on the understanding of enzyme mechanism. This advance would make this much more widely applicable. The Methods in Enzymology cahpter should increase the interest in this method
Sectors Chemicals,Healthcare,Pharmaceuticals and Medical Biotechnology

URL https://doi.org/10.1016/bs.mie.2019.11.018
Description NSF(USA) Prospects in Neutron Scattering for the Biological Sciences. Alexandria VA USA Feb 20-22 2018
Geographic Reach North America 
Policy Influence Type Membership of a guideline committee
Description Contributions to Methods in Enzymology volume 634 2020 (Ed PCE Moody) 
Organisation Oak Ridge National Laboratory
Country United States 
Sector Public 
PI Contribution I was Editor of Methods in Enzymology Volume 634 This chapter Chapter Eight - Dynamic nuclear polarization enhanced neutron crystallography: Amplifying hydrogen in biological crystals Pierce et al (2020) DOI:10.1016/bs.mie.2019.11.018 and invited this chapter because of the visit
Collaborator Contribution This covers the subject of the visit to the USA, the work is entirely that of the authors
Impact as above https://doi.org/10.1016/bs.mie.2019.11.018 in addition https://doi.org/10.1016/bs.mie.2019.11.020 is partailly an outcome
Start Year 2019
Description ORNL -LC 
Organisation Oak Ridge National Laboratory
Country United States 
Sector Public 
PI Contribution We contributed expertise in the structure and mechanism of heme enzymes and the application of neutron crystallography to investigate these. We provided input into how the techniques of dynamic nuclear polarisation might be applied specifically to these (and other ) systems exploiting the paramagnetic properties of the iron in the heme group.
Collaborator Contribution ONRL are developing the technology and facilities required for dynamic nuclear polarisation in neutron protein crystallography. They provided expert and confidential briefings on the progress of this development. A beam-line scientist was allocated to me for a week to outline, discuss and plan means to develop the collaboration, I was granted access to administrators and the head of section to discuss and formulate was to support a collabortaion. They have also awarded me exploratory beam time and protein expression resources
Impact Beam time at ONRL has been awarded. The visit allowed me to assess the level of progress being made at ONRL on DNP and become familiar with the experimental set-up at the neutron crystallography beam lines at ONRL. Although a scheme to allow a PhD student to be funded by ONRL and registered at the University of Leicester was proposed and explored at length, the limitations imposed on funding meant this will not proceed for the moment. However, we are working on a proposal to support and place a Leicester-based PhD student in the ONRL laboratories for extended periods (e.g. 3 months at a time). This has strong support, but administrative hurdles remain. Subsequent to this visit I was invited to participate in a NSF-funded discussion workshop on the future of neutrons in biology held near Washington DC in February 2018
Start Year 2017