X-ray fragment screening is a high-throughput technique that involves soaking pre-formed protein crystals with fragment compound libraries, followed by X-ray diffraction analysis. Leveraging rapid data acquisition at synchrotron facilities and advanced computational tools such as Pan-Dataset Density Analysis (PanDDA), this method delivers exceptional sensitivity in detecting novel fragment binders. X-ray fragment screening enables direct observation of binding events at atomic resolution, making it a powerful tool for early-stage drug discovery and structure-based design.
Crystallographic Fragment Screening Workflow – from compound soaking to structure refinement
A Complete Solution for X-ray Fragment Screening
Evotec offers an end-to-end X-ray fragment screening platform, combining precision automation, advanced data analysis, and structural biology expertise to accelerate hit identification and support structure-based drug design.
Cutting-Edge Automation
- ECHO acoustic dispenser enables precise and miniaturized liquid handling
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Crystal shifter streamlines the crystal soaking and harvesting steps
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Automated X-ray data collection followed by PanDDA-enabled analysis on Evotec’s high-performance computing cluster
Broad Applications
- Suitable for challenging targets not amenable to conventional screening techniques
- Detects orthosteric and allosteric binders, including cryptic binding sites
- Enables early assessment of the druggability of novel protein targets
Proven Success
- Delivers a 5–10% hit rate across a wide range of targets
- High ligand efficiency supports fragment merging, growing, and expansion toward novel drug candidates
