2021 Volume 63 Issue 3 Pages 232-235
In recent years, fragment-based drug discovery（FBDD） has revolutionised the development of potent lead compounds against protein targets. This “start small, elaborate efficiently” approach promises to address many deficiencies of traditional medicinal chemistry. It has been used successfully by industry and academics, delivering several drugs to the clinic, and many more to late-stage clinical trials. Probably the most useful and informative technique for FBDD is X-ray crystallography, employed most effectively as a primary screen to detect the binding of fragment hits to protein target sites, while simultaneously elucidating binding poise and identifying possibilities for fragment development. Here we report the development of the Fast Fragment and Compound Screening（FFCS） platform at the Swiss Light Source（SLS）, an integrated next generation pipeline for crystal soaking, handling and data collection, which allows crystallography-based screening of protein crystals against hundreds of potential drug leads. We also report the release of the Smart Digital User（SDU） software at our PXI X06SA and PXIII X06DA beamlines. In combination with existing beamline software infrastructure, SDU enables fully automated data collection, and is used both in concert with our FFCS platform and is a tool that is available for all beamline users.
