Biology – Quantitative Biology – Biomolecules
Scientific paper
2011-12-13
Biology
Quantitative Biology
Biomolecules
Scientific paper
Electrical signaling via voltage-gated ion channels depends upon the function of the voltage sensor (VS), identified with the S1-S4 domain of voltage-gated K channels. Here we investigate some physical aspects of the sliding-helix model of the VS using simulations based on VS charges, linear dielectrics and whole-body motion. Model electrostatics in voltage-clamped boundary conditions are solved using a boundary element method. The statistical mechanical consequences of the electrostatic configurational energy are computed to gain insight into the sliding-helix mechanism and to predict experimentally measured ensemble properties such as gating charge displaced by an applied voltage. Those consequences and ensemble properties are investigated for variations of: S4 configuration ({\alpha}- and 3(10)-helical), intrinsic counter-charges, protein polarizability, geometry of the gating canal, screening of S4 charges by the baths, and protein charges located at the bath interfaces. We find that the sliding helix VS has an inherent electrostatic stability and its function as a VS is robust in the parameter space explored. Maximal charge displacement is limited by geometry, specifically the range of movement where S4 charges and counter-charges overlap in the region of weak dielectric. The steepness of charge rearrangement in the physiological voltage range is sensitive to the landscape of electrostatic energy: energy differences of <2 kT have substantial consequences. Such variations of energy landscape are produced by all variations of model features tested. The amount of free energy per unit voltage that a sliding-helix VS can deliver to other parts of the channel (conductance voltage sensitivity) is limited by both the maximal displaced charge and the steepness of charge redistribution by voltage (sensor voltage sensitivity).
Nonner Wolfgang
Peyser Alexander
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