The molecular mechanism of multi-ion conduction in K+ channels
Steered molecular dynamics (SMD) simulation method is applied to a fully solvated membrane-channel model for studying the ion permeation process in potassium channels. The channel model is based on the crystallographic structure of a prokaryotic K$^+$ channel-- the KcsA channel, which is a representative of most known eukaryotic K+ channels. It has long been proposed that the ion transportation in a conventional K+-channel follows a multi-ion fashion: permeating ions line in a queue in the channel pore and move in a single file through the channel. The conventional view of multi-ion transportation is that the electrostatic repulsion between ions helps to overcome the attraction between ions and the channel pore. In this study, we proposed two SMD simulation schemes, referred to `the single-ion SMD' simulations and `the multi-ion SMD' simulations. Concerted movements of a K-W-K sequence in the selectivity filter were observed in the single-ion SMD simulations. The analysis of the concerted movement reveals the molecular mechanism of the multi-ion transportation. It shows that, rather than the long range electrostatic interaction, the short range polar interaction is a more dominant factor in the multi-ion transportation. The polar groups which play a role in the concerted transportation are the water molecules and the backbone carbonyl groups of the selectivity filter. The polar interaction is sensitive to the relative orientation of the polar groups. By changing the orientation of a polar group, the interaction may switch from attractive to repulsive or vice versa. By this means, the energy barrier between binding sites in the selectivity filter can be switched on and off, and therefore the K+ may be able to move to the neighboring binding site without an external driving force. The concerted transportation in the selectivity filter requires a delicate cooperation between K+, waters, and the backbone carbonyl groups. To accomplish a concerted transportation, the occupancy state of the selectivity filter must be an alternative sequence of K+ and water molecules, i.e., a K-W-K-W or a W-K-W-K sequence.