Abstract
Pepide toxins isolated from the venom of cone snails, spiders, and centipedes potently block or modulate the function of voltage-gated sodium channels (NaVs) essential for neuronal signalling. The high selectivity of these peptides for particular human NaV subtypes makes them ideal candidates for rational drug development. However, the precise binding locations and mechanisms of channel modulation remain undetermined. Here, experimental structural biological techniques will be combined with atomic detail molecular simulation methods to reveal the toxin binding sites and gain insights into their mechanisms of action. This information will ultimately guide the rational design of gain-of-function peptides for biomedical applications.
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