Small molecules are frequently used both in nature and therapeutically to modulate the activity of the protein they bind to. Yet, many aspects of small-molecule:protein interactions are surprisingly poorly understood. For instance, ligand polypharmacology, i. e. binding to multiple proteins, often comes as a surprise, although frequently it is precisely the reason for a drug's efficacy or its side effects. On the protein side, a point mutation in the binding site, although only a small change, can abolish drug binding, leading to resistance. Thus, it is highly relevant to develop a comprehensive understanding of small-molecule:protein interaction profiles in molecular detail and correlate these profiles with signaling and metabolic pathways.
Our main tool is small molecule docking, but we also use chemoinformatic approaches and molecular dynamics. The research spans method development, basic research and applications. Currently the investigations deal with kinases and G-protein coupled receptors (GPCRs).