The Structural Biology group is central to the operation of the DDU. Responsible for fragment-based hit identification, this group provides expertise across protein production, NMR, SPR, ITC and X-ray crystallography. Depending on the target, a primary fragment screen will generally be carried out using either NMR or SPR. The resulting initial hits are then validated using an orthogonal biophysical technique before being progressed through the screening cascade.
NMR-based fragment screening employs a state-of-the-art 600Mhz NMR with cryo-cooling and sample changer. In addition, a 400MHz instrument with sample changer is available for day-to-day chemistry/small molecule NMR.
SPR (surface plasmon resonance) provides valuable information on both the stoichiometry and the kinetics of ligand binding to protein targets. These are fundamental characteristics that can critically inform validation as well as prioritisation of hits. For high-throughput screening we use a state-of-the-art Biacore 8k instrument, while a Biacore T200 is available for more exploratory work.
The X-ray crystallography group generates high-resolution structural information to better understand the interactions between target proteins and small molecule ligands and thus drive compound design through all stages of a drug discovery project. The work is integrated with computational and medicinal chemistry to maximise the impact of the structural data and exploit a range of structure-based design methods. Our crystallographic work is enabled by a TTP Labtech Mosquito liquid handler, FORMULATRIX imagers/hotels, and ready access to synchrotron light sources. Additionally, the Structural Biology group has the opportunity to work with the research groups and facilities of Danny Huang and Shehab Ismail as well as groups at Glasgow University.
Justin Bower (Joint Head of Drug Discovery - Head of Structural Biology)