Computer-Aided Modelling in Crystallographic Drug Discovery

DASHH Doctoral Researcher: Thorben Schulze

Supervisors: Dr. Alke Meents (DESY), Prof. Matthias Rarey (UHH)

In the early stages of modern drug discovery, fragment-based approaches gained more importance over the last years. While in the classic HTS (High Throughput Screening) approach, a large library of potentially complex drug candidates gets tested against a clinically relevant target, in fragment-based drug discovery, smaller molecules get used. The binding of these fragments can be detected by using X-ray crystallography. This technique enables structure determination of protein crystals exposed to the compound. Binding fragments then get extended to suggest potent candidates for further research. This approach shrinks the search space compared to HTS, and the smaller molecules have higher optimization potential. Computational methods are used in these stages to make detecting binding events easier and propose extensions for found candidates. These candidates may get tested for bioactivity in further experiments.