The K04 XChem flagship builds on the success and oversubscription of the XChem fragment screening facility, developed in tandem with the evolution of beamline I04-1. The facility provides a world-unique offering for structure-based drug design, which is in heavy academic and industrial demand, with the resilience to support significant COVID work during lockdown.
The Diamond-II machine configuration necessitates removing beamline I04-1, providing the opportunity to rebuild it on the new K04 straight, delivering a beamline of vastly increased flux and brilliance, along with extreme automation. The resulting order-of-magnitude increase in throughput will fundamentally shift the scientific scope of crystallographic fragment screening. On the one hand, a far larger range of classes of drug targets will become viable, even when diffraction is weak. On the other hand, routinely large experiments will help achieve the coming revolution in rational drug discovery, by allowing all key interactions and conformations to be observed in 3D up front, providing the raw data that future algorithms will be able to exploit to design clinic-ready drug candidates from scratch.
A proof-of-concept demonstration of how ultra high throughput XChem would assist this long-sought but ever more realistic ambition, came from recent COVID-19 XChem experiments. The rich data from a very large screen was key to the premise of the COVID Moonshot, namely to rapidly achieve antiviral pre-clinical candidates. Supporting methodologies are in active development through several strategic partnerships, including the Rosalind Franklin Institute (Next Generation Chemistry theme), EUbOpen, and the Fragalysis project.
For more information on this proposed new beamline, click the button below to download the Full Science Case:
If you would like to keep up to date on K04/XChem Working Group progress and would like to receive updates by email, please sign up to the K04/XChem Flagship Interest Group by clicking the button below:
You are welcome to contact the project lead Frank von Delft, or chair of the User Working Group John Barker, with any questions or further feedback.
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