Voltage-gated sodium (Nav) channels are essential for electrical signaling in excitable tissues, including the brain, heart, and muscles. By transitioning between closed, open, and fast-inactivated states, they regulate sodium ion flux across the membrane and initiate the firing of nerve and muscle cells. Nav channel dysfunction underlies a range of diseases such as epilepsy, cardiac arrhythmias, paralysis, and genetic pain disorders, which are often treated with small molecule compounds that inhibit the pore.

My PhD applies molecular dynamics simulations to examine how Nav channels interact with modulatory molecules, including pore-blocking drugs and endogenous lipids, as well as how they are altered by disease-causing mutations. This talk will focus on three projects:
1. Small molecule inhibition - mapping the binding modes a diverse range of drugs bind in the Nav channel pore and membrane-facing fenestrations.
2. Phosphoinositide binding - uncovering the molecular mechanism by which this membrane lipid enhances Nav channel inactivation.
3. A severe epilepsy-causing mutation - revealing its impact on disrupting the Nav channel inactivated state.