Voltage-dependent potassium channels open in response to changes in membrane potential and become partially inactivated upon binding of inhibitors. Here we calculate normal mode motion of two voltage-dependent K(+) channels, KvAP and Shaker, and their complexes with inhibitors and address the gating principle, opening mechanism, and inhibition. The normal modes indicate that pore expansion and channel opening is correlated with a displacement of the arginine gating charges and a tilting of the voltage-sensor paddles. Normal modes of Shaker in complex with agitoxin, which blocks the central pore, do not display significantly altered paddle tilting and pore expansion. In contrast, normal modes of Shaker in complex with hanatoxin, which binds to the voltage sensor paddle, display decreased paddle tilting and pore expansion. This study presents a unified motion for the gating principle and channel opening, and offers insight into the voltage sensor paddle motion and its inhibition.
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