Fragment Screening (XChem)

XChem fragment screening

Users have access to a full fragment screening platform, from high-throughput soaking of compounds and harvesting of crystals in the XChem lab (lab 34) to unattended data collection with dedicated beamtime on I04-1. Users will be trained to use a software pipeline for data analysis of weak fragment binders in hundreds of datasets.

The XChem lab is equipped with:

• More than 2000 compounds from several different libraries, or we can accommodate your own library
• 2 ECHO acoustic liquid dispensers (Labcyte) for very fast and accurate transfer of compounds
• 3 crystal harvesting stations (called the “shifter”)
• Dedicated and barcoded pucks and size-sorted pins
• SQLite database for the repository of compounds and experiments 

As standard in Diamond MX beamlines, I04-1 is equipped with:

• BART sample changer (592 samples)
• Unattended data collection with automatic sample centring (X-ray or optical)
• Fully automated auto-processing pipelines (fast_dp, Xia2, DIALS and autoproc)
• ISPyB webserver for following data collection and processing progress

XChem software pipeline:

• XChemExplorer (XCE) for fragment screening data management and workflow tool for data analysis (Krojer, T. et al. 2017, Acta Cryst D 73, 267–278)
• PanDDA, Pan-Dataset Density Analysis (PanDDA) method for the detection and identification of weak binders (Pearce, N. et al, 2017, Nature communication)

Specific to XChem:

• Weekly 24-hour dedicated beamtime

Fragment screening is part of the Signature Access drug discovery access route in iNEXT DIscovery.

Dr Daren Fearon: daren.fearon@diamond.ac.uk

Dr Frank von Delft: frank.von.delft@diamond.ac.uk

Achieving Efficient Fragment Screening at XChem Facility at Diamond Light Source

iNEXT DISCOVERY workshop on crystallographic fragment screening

1st - 3rd March 2023

Link to webpage