Fragment Screening

Optimised screening cascades to accelerate lead development

The development of biophysical techniques with sufficient sensitivity and throughput to enable fragment screening is a key innovation enabling FBD to flourish. While a primary fragment screen may result in hundreds of hits, there is often only sufficient resources to initiate a medicinal chemistry development program on only the “best” two or three of these.

Therefore, it is essential to have robust strategies to prioritise fragments for further investigation. In collaboration with our industry partners, we will evaluate different strategies for fragment hit ranking and validation to optimise the fragment screening process.

On-going projects:

  • Development of automated analysis of biophysical screening data (NMR, SPR and X-ray crystallography)
  • New NMR methods to characterise the ligand binding modes in protein-ligand complexes not amenable for X-ray crystallography
  • NMR dynamics in ps-s time scales for investigating the structural origins of cryptic sites on proteins
  • 3D structure determination of peptides and proteins by solution NMR spectroscopy
  • Implementation/development of new NMR methods to support fragment-/structure-based drug design