Structure and Function of Voltage-Gated Ion Channels and their Applications for Rational Drug Design

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Sodium channels are membrane proteins which enable the regulation and flow of sodium ions across cell membranes. They are found in all eukaryotic organisms and a range of bacteria. In humans they exhibit a wide range of functions in the healthy organism, and are the targets for many pharmaceutical drugs for treatment of neurological and cardiac diseases. In insects they are the target sites of many insecticides, and also the source of development of resistance. This proposal is to determine the crystal structures of a number of natural and mutant sodium channels and related ion channels, and compare their structures with functional studies to better understand the means by which the channels open and close and selectively translocate sodium ions. By examining complexes of these channels with actual and potential drugs and ligands, this should enhance the rational development of new and highly specific insecticides and pharmaceuticals.