Diamond’s on-site fragment screening facility is a major boost for structural biologists
The crystal structure, Pneumolysin, published in the journal Scientific Reports, represents a significant milestone for Diamond. Pneumolysin is the 3,000th protein structure to be solved at the facility and deposited in the Worldwide Protein Data Bank since Diamond came online in 2007. (L-R): Frank Von Delft (Diamond Light Source, Principle Beamline Scientist I04-1), John Barker (Evotec), Professor Dave Stuart, (Diamond’s Life Sciences Director), Peter Moody, Russell Wallis, and Peter Andrew from Leicester University
Scientists developing new medicines to treat a wide range of diseases now have access to a world-first facility based at Diamond Light Source – the UK’s national synchrotron science facility – for accelerating the process of developing novel compounds for drug discovery.
The new XChem facility at Harwell Science and Innovation Campus will be available to academic groups and drug development companies so that they can speed up the early stages of drug design.
Prof Dave Stuart, Diamond’s Director of Life Sciences and Head of the Division of Structural Biology in the Department of Clinical Medicine at the University of Oxford, said: 'Scientists are using Diamond to study a range of viral and bacterial infections, along with cancer, heart disease, diabetes and neurodegenerative conditions such as Alzheimer’s and Parkinson’s.
'While great progress is being made, on average it still takes at least ten years for a new medicine to complete the journey from initial discovery to the marketplace.
'Having a facility like XChem at the synchrotron is therefore a major step forward, allowing scientists to evaluate the equivalent of millions of compounds using just a few hundred much smaller compounds (also called fragments).'
Though well-established, the screening technique has not so far been available in a central facility location to scientists from across the UK and abroad. Moreover XChem introduces a step-change in the sensitivity of the experiment, by harnessing synchrotron X-rays so that fragments can be directly observed interacting with the target protein. This allows structural biologists to identify where drugs could potentially bind, to target that particular area for further research.
Having a facility like XChem at the synchrotron is a major step forward
The duration of the experiment has also been reduced from months to days by new technologies developed at Diamond and in partnership with the Structural Genomics Consortium at Oxford University.
Dr Frank von Delft, jointly head of the XChem facility and the partnering lab at Oxford University, said: 'It is only a world-class national synchrotron like Diamond that makes such a facility conceivable, and it is its strong collaborative links with the UK’s universities that then leads to the creation of next-generation technologies like XChem.'
John Barker, Vice President Structural Biology at Evotec, which worked with Diamond to deliver the XChem platform, added: 'Evotec and Diamond have worked closely to deliver the XChem platform for rapid identification of novel starting points for drug discovery campaigns for the drug discovery community.
'The new fragment-based discovery platform complements the breadth of techniques available at established companies, such as Evotec, while opening a new path to discovery for academic groups. Evotec is already making use of the XChem facility. Although details remain confidential for these early drug discovery campaigns, invaluable information is helping to progress multiple therapeutic targets for our international collaborators.'
A recent discovery that has the potential to benefit from the fragment screening facility has been led by a team of scientists from the University of Leicester. They have successfully solved the structure of the elusive protein pneumolysin. This toxin, which is secreted by Streptococcus pneumoniae bacteria, is capable of killing cells. In doing so, it helps these bacteria, which are responsible for a range of serious illnesses including pneumonia, meningitis and septicaemia, to take hold in humans.
Funded by the Wellcome Trust and the Medical Research Council, the University of Leicester research was led by Professor Russell Wallis of the Departments of Infection, Immunity and Inflammation and Molecular and Cell Biology and Professor Peter Andrew, Head of Department of Infection, Immunity and Inflammation. The crystal structure, published in the journal Scientific Reports, also represents a significant milestone for Diamond.
Pneumolysin is the 3,000th protein structure to be solved at the facility and deposited in the Worldwide Protein Data Bank since Diamond came online in 2007.