XFBLD-Platform: a crystallographic fragment-screening platform at Shanghai Synchrotron Radiation Facility.

Abstract

Fragment-based lead discovery (FBLD) is an efficient and effective method for identifying novel chemical scaffolds that have advantages in drug development. X-ray crystallography has an inherent advantage in recognizing low-affinity fragments and integrates fragment identification with complex structure determination, making it an increasingly important tool for screening fragment compounds. Here, we introduce a crystallographic fragment-screening platform developed by the biological macromolecular crystallography group at Shanghai Synchrotron Radiation Facility, named the XFBLD-Platform. This platform promotes fragment-based lead discovery through a comprehensive workflow that includes high-throughput complex crystal preparation, crystal harvesting, diffraction data collection and analysis, and fragment-affinity estimation. It integrates advanced hardware, high-performance beamline facilities and specialized experimental design and data-management software. The platform provides a rapid and practical approach for structure-based drug development.