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.
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