Potassium channels are highly specific membrane-spanning protein structures which facilitate and regulate the passage of K+ ions across the lipid barrier, giving rise to the electric signals that underlies a variety of cell functions. Although several families of potassium channels have been identified, a prokaryotic channel from Streptomyces lividans (KcsA) is the only one whose structure has been determined by X-ray crystallography to high resolution (2.0 A). As increasing efforts are devoted to the structural characterization of ion channels, the neurotoxins which bind at the extracellular vestibule of potassium channels with high specificity can serve as powerful investigative tools. In the proposal we plan to study the interactions between potassium channels and their specific yet divergent neurotoxins by modeling their complex structures using molecular dynamics simulations aided with experimental mutagenesis data. The goal of this research proposal is to improve our understanding of the principles governing the interactions of neurotoxins with potassium channels and the molecular basis for their specificity using atomic models derived from modern computational calculations.
Our aim with these calculations is to complement the information that is currently available from experiments and, and through this work, refine our knowledge of ion channels. Lastly, a tool-box of systematic computational methods for analyzing structural models of toxin-channel complexes will be developed and made available to the scientific community.
