The influence of dynamics of ionic channel protein on its selectivity function

Computer simulation was applied for modelling the sodium channel selective filter. The geometric parameters, electrostatic interactions and channel protein polar group dynamics were studied with respect to their effect on permeability and selectivity function. The most important parameters were shown to be the filter width, electrical charge on the binding site and the dielectric constant. Appropriate selection of all three parameter values permitted a qualitative description of the experimentally obtained data on Na+ channel selectivity. The dynamics of the dipolar groups in the channel protein molecule were treated in terms of the Debye model of dipolar relaxations. The dynamics of the dipoles exerted the most significant effect on channel permeability and selectivity. It is shown that when the dynamics occur on a scale slower than that of the motion of ions, the channel will exhibit a low degree of permeability and its selectivity will be lost. The model predicts the appearance of an effect arising from the saturation of electric current with increasing concentration of the permeant ion species. The saturation current decreases at slower rates of dipolar relaxation. Therefore, the effective operation of ion channels requires the channel protein to be capable of undergoing rapid motion.