Center for Biomolecular Structure Lecture Series

In 2023, the Center for Biomolecular Structure (CBMS) at the National Synchrotron Light Source II (NSLS-II) at Brookhaven National Laboratory, Upton, NY, USA began offering access to an x-ray crystallographic fragment screening facility (XCFS) to the CBMS MX user community. The platform provides users with the full stack of lab equipment necessary to go from purified protein to hit structures. Briefly, crystals are grown with microseeding protocols using a multi-channel contact pipetter, fragments from commercial libraries are added to crystallization drops with acoustic droplet ejection, soaked crystals are harvested with a crystal shifter and diffraction data are collected at the AMX beamline (17-ID-1) in fully automated mode. The NSLS-II XCFS facility offers approximately 2000 fragment compounds with the ability to plug in custom follow up compounds, and x-ray diffraction datasets are collected at a rate of approximately 600 samples/day with a fixed 7x5 micron beam and raster-based centering. To date the facility has processed over 20 projects and generated thousands of datasets. This new resource creates new challenges and opportunities for the modeling and distribution of protein structures in complex with weakly bound fragments.