The chemical-physical basis for K+ permeation and selectivity in K+ channels has been the focus of attention of many theoretical and computational studies since the first crystal structure was obtained by the Mackinnon lab in 1998. Most of the previous studies reported focused on atomic descriptions of permeation events in the selectivity filter of K+ channels in their closed conformation. In this Article, a comparative analysis of permeation events in the KirBac1.1 K+ channel in a closed- and an open-state model is presented. The availability of models of the same channel in two different conformations has made this comparative analysis possible. All-atom molecular dynamics simulations of both models in a membrane environment have been carried out. As previously suggested by many studies of this and other K+ channels, when the channel is closed the ion conduction involves transitions between two main sites of the selectivity filter, with two K+ ions each coordinated by eight carbonyl oxygens of the protein and separated by a water molecule. In contrast, in our open-state model, three to four K+ ions move in a concerted motion during the permeation process. The selectivity filter, though maintaining a certain degree of flexibility to cope with these cooperative events, appears to be more “symmetrical” and robust in the simulations of the open-state channel when it is occupied by an average of three ions. Therefore, it appears as if the occupation of the pore depends upon the global conformation of the channel. Due to the complexity of these systems, only single conduction events have been described by means of molecular dynamics trajectories. To complement these results and describe the energetics of ion permeation and ionic fluxes, continuum approaches (Poisson−Boltzmann and Poisson−Nernst−Planck theory) have been also employed.
- Computer Simulation, Ion Channel Gating, Ions, Lipid Bilayers, Models, Biological, Permeability, Phosphatidylcholines, Potassium Channels, Protein Conformation, Time Factors, Water