Fragment-Based Drug Discovery

Head: Grzegorz Popowicz

A new fragment-based drug discovery (FBDD) screening facility has commenced operation in May 2013. Integrated into the Institute of Structural Biology (STB), the facility uses specialized high-throughput NMR equipment to search for small molecules, called fragments that have biological and potentially therapeutic activity. Fragments are molecules typically 2-3 times smaller in size than drug molecules. Individually, they possess only limited activity, yet upon merging of several fragments, very potent drug candidates can be designed. The FBDD facility uses NMR to detect fragment-protein interactions. High throughput automation allows screening of the complete library in a fully automated mode in a couple of days. The facility does not only screen for active fragments but also uses chemoinformatic methods to design and produce novel drug candidates. Moreover, NMR based methods are available and used to validate hits from HTS assays.

Portfolio

  • Consulting and help in planning HT fragment screens optimized for target protein
  • Performing screening of the chemical libraries for target protein binding
  • Validation of the hits
  • Binding site mapping
  • Affinity estimation
  • Structural investigation of the protein-ligand complexes
  • Interpretation of the NMR binding data and help in further ligand optimization


Technology

  • 600 MHz NMR Spectrometer for high resolution protein spectroscopy
  • Cryogenically cooled probe for extreme sensitivity
  • Curated library of 1500 samples
  • Sample Jet automation allowing 500 samples to be measured w/o operator intervention
  • Gilson liquid handler to prepare samples for NMR automation
  • Fluorescence-polarization secondary assays
  • Portfolio of specially optimized experiments for measuring protein-ligand operation
  • Custom-developed data analysis software
  • Sample preparation laboratory