Diamond Annual Review 2023/24

57 D I A M O N D L I G H T S O U R C E A N N U A L R E V I E W 2 0 2 3 / 2 4 The team has also delineated plans for the Diamond-II flagship beamline K04, which will further increase sample throughput up to 10,000 samples a day, aiding further expansion of the XChem programmes and the incorporation of currently intractable projects. The project is divided into four sub-projects: Beam Delivery, Endstation, Automated XChem Laboratory (AXL), and Software. The Technical Design Review (TDR-A) document for the Beam Delivery arm of the project is complete, and TDR-B is in progress. For the AXL Project, drafting of the relevant documentation is underway andwork on the XChemAutomated CrystalTransfer (X-ACT) system, which aims to fully automate crystal harvesting, has begun. The XChem team and collaborators published an article in the journal Science detailing the open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors as part of the COVID Moonshot and have presented work fromtheir National Institute of Health funded anti-viral drugAntiviral Drug Discovery Centers for Pathogens of Pandemic Concern (the AI-driven Structure- enabled Antiviral Platform (ASAP) and the Rapidly Emerging Antiviral Drug Development Initiative (READDI)) at various conferences around the world, including the IUCr 26th Congress in Melbourne, the iNEXT Discovery Annual Meeting in Budapest and the Royal Society of Chemistry’s 9th Fragment-based Drug Discovery Meeting in Cambridge. Key publications: - Boby, M.L. et al ., Open science discovery of potent noncovalent SARS- CoV-2 main protease inhibitors, Science (2023). DOI : 10.1126/science.abo7201 - Chenthamarakshan, V. et al. Accelerating drug target inhibitor discovery with a deep generative foundation model, Science Advances, (2023). DOI: 10.1126/sciadv.adg7865 - Huseby D.L. et al . Antibiotic class with potent in vivo activity targeting lipopolysaccharide synthesis in Gram-negative bacteria, PNAS, (2024). DOI: 10.1073/pnas.2317274121 XFEL-Hub The XFEL Hub at Diamond continues to provide expertise and support to the UK community engaged in serial crystallography and XFEL-related life science research. This ranges from experimental conception to beamtime proposals, through sample preparations and testing, to XFEL data collection, analysis, and publication. Our Diamond-based activities continue to include organizing and running the block allocation group “Dynamic Structural Biology at Diamond and XFELs” for serial crystallography and time-resolved studies at various MX beamlines at Diamond. The XFEL-Hub also contributed to identify the structure of a ribonuclease reductase protein. As this protein carry radicals to catalyse biochemical reactions, researchers wanted to characterise the structure of the protein with the radicals intact. Diamond’s XFEL Hub contributed to this project by helping create a novel sample delivery strategy to rapidly deliver tiny droplets of amicrocrystal slurry of R2 protein to the X-ray interaction region. Like an assembly line in a factory, the microcrystals are shuttled along a conveyor belt called a ‘tape drive’ towards the X-ray beam. The major advantage of this system was that the sample delivery and chamber environment could be controlled to avoid neutralizing the radical. The X-FEL experiments were performed at the Linac Coherent Light Source. The Active Materials Laboratory In 2019 Diamond was awarded a grant by the EPSRC to build an Active Materials Laboratory at the synchrotron as part of the National Nuclear User Facilities II scheme to provide more research facilities for nuclear researchers in the UK. The principal aim of this laboratory is to enable Diamond users to handle active materials on site, either in the short term or performing longer term experiments. All beamline samples will be contained before studying them on one of Diamond beamlines. Before the laboratory was built nearly all radioactive samples had to be brought to site in the containment in which they were going to be measured on the beamlines. This, in particular, made doing experiments inwhich the sample was heated or exposed to gases on a beamline difficult as the whole cell had to be transported intact. The areas of research that the laboratory will benefit include materials for new nuclear fission, long-term storage of nuclear materials, a geological disposal facility for medium and high activity waste, how radionuclides behave in the environment and materials for nuclear fusion. The building was constructed over the period of October 2020 – July 2021, before a fit out that was extended because of various Covid-related supply issues. The lab is now complete. It consists of two working labs, one nominally The XChem/I04-1 team and collaborators at the AI-driven Structure-enabled Antiviral Platform (ASAP) meeting in New York.