Dr Gabi Heller

BBSRC Discovery Fellow (University College London) and CEO/CSO (Bind Research)

Research summary

Intrinsically disordered proteins are highly dynamic biomolecules that rapidly interconvert among many structural conformations. These dynamic proteins are involved in cancers, neurodegeneration, cardiovascular illnesses, and viral infections. Despite their enormous therapeutic potential, intrinsically disordered proteins have generally been considered undruggable because of their lack of classical long-lived binding pockets for small molecules. Currently, only a few instances are known where small molecules have been observed to interact with intrinsically disordered proteins, and this situation is further exacerbated by the limited sensitivity of experimental techniques to detect such binding events. We use all-atom metadynamics simulations and nuclear magnetic resonance spectroscopy to characterise the interactions between small molecules and intrinsically disordered proteins towards the discovery and development of new therapeutics targeting these highly dynamic biomolecules.

Keywords

Intrinsically disordered proteins, drug discovery, all atom molecular dynamics simulations, metadynamics