Ion conduction in K+-channels is usually described in terms of concerted movements of K+ progressing in a single file through a narrow pore. Permeation is driven by an incoming ion knocking on those ions already inside the protein. A fine-tuned balance between high-affinity binding and electrostatic repulsive forces between permeant ions is needed to achieve efficient conduction. While K+-channels are known to be highly selective for K+ over Na+, some K+ channels conduct Na+ in the absence of K+. Other ions are known to permeate K+-channels with a more moderate preference and unusual conduction features. We describe an extensive computational study on ion conduction in K+-channels rendering free energy profiles for the translocation of three different alkali ions and some of their mixtures. The free energy maps for Rb+ translocation show at atomic level why experimental Rb+ conductance is slightly lower than that of K+. In contrast to K+ or Rb+, external Na+ block K+ currents, and the sites where Na+ transport is hindered are characterized. Translocation of K+/Na+ mixtures is energetically unfavorable owing to the absence of equally spaced ion-binding sites for Na+, excluding Na+ from a channel already loaded with K+.
- molecular dynamics, potassium channels, umbrella sampling, potential of mean force, free energy, POTASSIUM-CHANNEL, MOLECULAR-DYNAMICS, POTENTIAL FUNCTIONS, K+/NA+ SELECTIVITY, BINDING-SITES, KCSA CHANNEL, CONDUCTION, ENERGY, FILTER, WATER