Open and Shut Case Voltage-sensing domains (VSDs) control the activity of voltage-gated ion channels to regulate the ion flow that underlies nerve conduction. Structural and biophysical studies have provided insight into voltage gating; however, understanding has been hindered by the lack of a crystal structure of a fully closed state. Starting from a structure of an open conducting state, a voltage-gated K + channel, Jensen et al. (p. 229 ) used all-atom molecular dynamics simulations to show the conformational changes involved in switching to the closed, nonconducting state. Additional simulations revealed the major steps of channel activation. The computational determination of a closed state may guide development of drugs to treat channelopathies associated with this resting state.