About SFB-F3502

Molecular basis of drug-transporter interaction

For membrane bound proteins only a very limited number of structures have so far been resolved in atomic resolution. Thus, very often 3D-models based on the structures of homologous proteins are used in order to get first insights into the molecular basis of ligand binding. In case of ABC-transporter and biogenic amine transporter recently published X-ray structures represent versatile templates for generation of protein homology models. Within the project we will use a combination of ligand-based design approaches and docking to homology models to explore the interaction of drugs with the transmembrane transporters ABCB1, SERT and GAT1 on the molecular level. Taking into account the polyspecificity of the proteins, docking poses will be thoroughly validated by photoaffinity labelling, mutagenesis and ligand-based SAR studies. The final binding site hypotheses will be used for in silico screening of large compound libraries in order to obtain new chemical scaffolds active on the respective transporter.

Gerhard F. Ecker