Docent lecture: Structural dynamics of voltage-gated ion channels and implications for health and disease


Electrical signals are important for biological function. They enable for example the brain, heart and muscles to function properly. They are also involved in cellular replication, with implications for cancer propagation. The proteins responsible for ion transport through the membrane and transmission of electrical signals are called voltage-sensitive ion channels. Their function depends in part on their structure, which is known since the early 2000s. Nevertheless, we still lack a detailed understanding of their dynamic behavior as well as the structural ensemble that make up their functional cycle. These are critical for designing innovative and targeted modulation for pharmaceutical development.
In this lecture, I will explain how we use molecular dynamics to characterize the structural ensembles of voltage-sensitive ion channels at the atomic level. I will also show that closely related voltage-sensitive ion channels behave more differently than we originally believed. These insights extend the understanding of disease-inducing genetic mutations, their effect and will enable the design of drugs that modulate the function of these channels.