Voltage-sensor domains (VSD) are 4-helix transmembrane (TM) regulatory domains that undergo a conformational change in response to a change in the TM potential. Coupled to a pore, they form a voltage-gated ion channel. Our work focuses on revealing the molecular-level functional mechanism of such domains and the transduction of the signal to the ionic pore.
Starting from the activated state crystal structure of Kv1.2, a Shaker family voltage-gated channel, we have used molecular dynamics simulations to decipher the deactivation pathway. We have also characterized the free energy profile of the process using enhanced sampling techniques. This work helps to understand how such this protein transfers an electrical signal so efficiently.