Quantitative understanding of protein-ligand interactions
FKBP51 is a superb model system for fundamental studies on rational drug design. It can be obtained in large amounts, is well behaved and amenable to all major biophysical techniques. We routinely obtain cocrystal structures at extraordinary resolution (>20 structures with <1.2Å). However, this structural information cannot be straightforwardly correlated with the affinity of the ligands. We are currently developing novel methods to explore the energetic of ligand-protein contacts at single-atom resolution as a basis to improve binding energy predictions.