X-ray based drug design platform

Structure-based drug design is a corner stone of modern drug discovery, where structural information on protein-compound complexes is explored in the design of pharmaceutical drugs.

X-ray screening is an attractive approach to identify initial hits to be used as starting points that can be further developed into potent pre-clinical compounds.

However, there are three major limitations today hindering the full exploitation of X-ray screening in drug discovery; the manual intervention required in the handling of crystals and X-ray data collection which severely limits the throughput, and the challenges associated with expanding initial hits into highly potent drug-like compounds.

Through this project we will develop novel approaches to overcome these three challenges.

We will design new multi-crystal sample holders for efficient X-ray diffraction experiments in combination with highly automated data processing routines, and advanced computational methods for extension/optimization of initial hits into pre-clinical compounds.

Finally, the developed pipeline will be applied to two concrete drug discovery projects for future treatment of covid 19 and the neglected tropical disease lymphatic filariasis.

This project is a close collaboration between leading structural biology groups at the University of Gothenburg, AstraZeneca, the University of Hamburg and scientists at MAX IV Laboratory, Petra III and EU-XFEL.