Fragment Screening at (Almost) the Speed of Light

The XChem facility offers drug discovery scientists streamlined, highly sensitive fragment screening, by harnessing the power of synchrotron light.

By Frank von Delft

My vague awareness, as an undergraduate in my native South Africa, that structural analysis could help create new drugs, was given direction by the offer of PhD research with Tom Blundell, a world-leading figure in X-ray crystallography at Cambridge. However, it didn’t take long to notice that despite the tremendous power of X-ray crystallography, it was hamstrung by inefficiency. The questions I address now in high-throughput crystallography are often as much scientific as engineering challenges: how can we streamline processes and put the right infrastructure in place to fulfill the promise of the technique?

Currently, I have two roles. At Oxford University, I am part of the not-for-profit Structural Genomics Consortium (www.thesgc.org) – a public–private partnership that started off trying to facilitate compound development by solving structures of medically relevant proteins and placing them in the public domain, but has since moved to actively generating probe molecules. There, as head of the protein crystallography group, it’s my job to make sure that my colleagues can do the crystallization and X-ray experiments they need, as efficiently as possible – methodology is my research focus.

Three years ago, I also became head of a beamline at Diamond Light Source, the UK’s synchrotron facility, a few miles south of Oxford. For the uninitiated, a synchrotron is a particle accelerator, speeding up electrons to near-light speeds to generate very bright beams of X-ray, infrared or ultraviolet light. Each beam, up to 10 billion times brighter than our sun, is focused into an experimental station – the beamline. Beamlines around the world support a huge range of disciplines, but researchers in macromolecular crystallography have always been scientifically prominent users.

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