Fragment Screening at Diamond
At Diamond beamline I04-1, the full X-ray screening experiment has now been implemented as a highly streamlined process, allowing up to 500 crystals to be soaked and harvested in a day, and collected in 24 hours beamtime. The process covers soaking, harvesting, automatic data collection, and data analysis; and fragment libraries are available, or users can bring their own.
This is available to both academic and commercial users but the application process is different.
If you are interested there is a very useful checklist that should simplify the process.
The facility is based at beamline I04-1 and nearby Lab 36, where the soaking and harvesting is performed.
In practice, the experiment will span a few days and even multiple visits to establish crystals' suitability. Users must generate the crystals in their home lab, and are required to come and perform soaking and harvesting themselves: multi-day Lab Visits will be scheduled separate from normal beamline time. In contrast, users do not need to be present for the X-ray data collection, although they are asked to help monitor (remotely) the automated collection when it occurs. A local contact will be assigned, same as for beamtime.
In practice, the first steps to unsure reproducibility are iterative and require a few dozen crystals, and in difficult cases even several Lab Visits; but associated diffraction testing will be fitted in during the Lab Visit where possible. The final "Full run" soaking and harvesting will be scheduled once the soaking protocol is confirmed (in favourable cases during the same Lab Visit).
Data analysis builds on the existing automatic data processing, and we are developing tools to streamline density interpretation and refinement, analysis and presentation of hit results, and depositing hit structures. Use of these tools is optional, but feedback valued: they will be deployed on Diamond's compute environment as they become available.
The Diamond fragment collection is actively evolving from the original Maybridge fragment collection, on the one hand to eliminate compounds that are poorly soluble, unstable or systematically kill crystals. On the other hand it is being expanded with synthesis-ready compounds.