The human Nav1.1 sodium channel: Structure, Function, Drug Binding and Molecular Dynamics of Homologues Bearing Disease-Related Mutations

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Voltage-gated sodium channels (Navs) play essential roles in nerve signal transmission, as their opening initiates the action potential. Mutations in the human hNav1.1 isoform produce a range of diseases, including epilepsy. hNav1.1 therefore represents a key target for pharmaceutical drug development. Using the prokaryotic NavMs (whose crystal structure we have determined), which has highly similar structural and functional properties to hNav1.1, the student will create mutants associated with hNav1.1 diseases, and examine their effects on a molecular level using crystallography, cryoEM, molecular dynamics calculations, and biophysical, biochemical, and functional characterizations, using this information to explore potential new drug candidates.