Linking dynamics of ion channels with biological function

Ion channels are membrane proteins, regulating biological processes by controlling passive ion flux across cell membranes. With more than 60 ion channel diseases identified to date, ion channels have great potential for the treatment of disease. Several drugs that modulate ion channels are in clinical use. Owing to the complexity of these channels and the lack of 3D structures, rational drug design is challenging. For most ion channels no specific ligands have been identified. Another complicating factor for drug development arises from the fact that ion channels undergo conformational changes during gating, leading to different binding affinities and changes in binding site accessibilities. Thus, a better understanding of the structure, gating dynamics and molecular mechanisms underlying disease is urgently needed. My research addresses several of these fundamental questions including methods to develop accurate and reliable 3D structure models, investigations of gating mechanisms and analyses of drug receptor interactions.