Ass.Prof.Priv.Doz.Dr. Anna Weinzinger

Structural investigations of K+ ion channel gating and drug interactions.
Potassium channels play a critical role in numerous physiological and pathophysiological processes rendering them attractive targets for therapeutic intervention. The activity of K+ channels is controlled by dynamic conformational changes that regulate ion flow through the central pore of the channel. This process is known as 'gating', and understanding the molecular mechanism of these dynamic changes is critical to our understanding of how these channels function in both health and disease. For a recent computational study on gating dynamics of K+ channels see Linder et al, Plos Computational Biology, 2013. Importantly, gating can also lead to changes in drug binding sites and thus modulate drug affinity. Thus, the aim of the current project will be to investigate gating induced changes in drug binding affinities. This project will be performed in close collaboration with chemistry (Nuno Maulide) and electrophysiology groups (Steffen Hering) of the consortium as well as international collaboration partners in the US and The Netherlands. Methods: The student will learn and apply the following computational techniques: molecular dynamics simulations of ion channel - drug complexes, free energy calculations, homology modeling and model refinement, pharmacophore modeling etc.