title: Computer simulation of the KvAP voltage-gated potassium channel: steered molecular dynamics of the voltage sensor.
abstract: The recent crystal structures of the voltage-gated potassium channel KvAP and its isolated voltage-sensing 'paddle' (composed of segments S1-S4) challenge existing models of voltage gating and raise a number of questions about the structure of the physiologically relevant state. We investigate a possible gating mechanism based on the crystal structures in a 10 ns steered molecular dynamics simulation of KvAP in a membrane-mimetic octane layer. The structure of the full KvAP protein has been modified by restraining the S2-S4 domain to the conformation of the isolated high-resolution paddle structure. After an initial relaxation, the paddle tips are pulled through the membrane from the intracellular to the extracellular side, corresponding to a putative change from closed to open. We describe the effect of this large-scale motion on the central pore domain, which remains largely unchanged, on the protein hydrogen-bonding network and on solvent. We analyze the motion of the S3b-S4 portion of the protein and propose a possible coupling mechanism between the paddle motion and the opening of the channel. Interactions between the arginine residues in S4, solvent and chloride ions are likely to play a role in the gating charge.
authors.affiliation: Department of Biological Sciences, University of Calgary, 2500 University Dr. NW, Calgary, AB, Canada T2N 1N4.
authors.forename: Luca
authors.initials: L
authors.lastname: Monticelli
authors.forename: Kindal M
authors.initials: KM
authors.lastname: Robertson
authors.forename: Justin L
authors.initials: JL
authors.lastname: MacCallum
authors.forename: D Peter
authors.initials: DP
authors.lastname: Tieleman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003198:Computer Simulation; D015640:Ion Channel Gating; D008958:Models, Molecular; D008969:Molecular Sequence Data; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D016415:Sequence Alignment
chemical_list: D024642:Potassium Channels, Voltage-Gated