Research

 Molecular modeling of ion channels

Our research focuses on ion channels, which are key molecules for signal transduction across cell membranes. Dysfunction of these proteins has been linked to many diseases (termed channelopathies), including arrhythmias, diabetes and various forms of cancer. Further, more than 70 rare channelopathies have been identified, each affecting only a small number of patients. A detailed mechanistic understanding of channel structure and dynamics, in particular of mutant induced dysfunction is crucial to understand their crucial roles in health and disease.

Recent progress in structural biology has provided us with static structures of many of these molecular machines, providing important insights into how these proteins may perform their function. Molecular dynamics simulations, which we run on high performance computers provided by the Vienna Scientific Cluster, allow us to simulate the motions of these proteins and to explore the relationship between (static) structure and dynamic function on the atomistic level.

A fundamental question is how inherited gain-or loss-of-function mutations affect the structure and dynamics of the channels and thereby normal channel function. To this end, we are performing extensive molecular dynamics simulations to elucidate conformational and dynamic changes caused by single-point mutations. A major goal is to identify specific modulators for different disease causing mutations, in particular to identify approved drugs, which are promising candidates for development of drug therapies for rare channelopathies. Hypotheses developed by our computational approaches are tested in close collaboration with experimental laboratories.

Publications:

• ORCID 0000-0002-9202-0484,
• Pubmed-NCBI
• u:cris