Energetics of ion conduction through the K+ channel

Abstract

K+ channels are transmembrane proteins that are essential for the transmission of nerve impulses. The ability of these proteins to conduct K+ ions at levels near the limit of diffusion is traditionally described in terms of concerted mechanisms in which ion-channel attraction and ion-ion repulsion have compensating effects, as several ions are moving simultaneously in single file through the narrow pore. The efficiency of such a mechanism, however, relies on a delicate energy balance-the strong ion-channel attraction must be perfectly counterbalanced by the electrostatic ion-ion repulsion. To elucidate the mechanism of ion conduction at the atomic level, we performed molecular dynamics free energy simulations on the basis of the X-ray structure of the KcsA K+ channel. Here we find that ion conduction involves transitions between two main states, with two and three K+ ions occupying the selectivity filter, respectively; this process is reminiscent of the 'knock-on' mechanism proposed by Hodgkin and Keynes in 1955. The largest free energy barrier is on the order of 2-3 kcal mol-1, implying that the process of ion conduction is limited by diffusion. Ion-ion repulsion, although essential for rapid conduction, is shown to act only at very short distances. The calculations show also that the rapidly conducting pore is selective.

Cooperative transport in a potassium ion channel

“…Ion mobilities and ion fluxes have been measured by Brownian dynamics simulations, [7][8][9][10] and the potential profiles and free energy surface of ions inside the pore have been calculated employing molecular dynamics [11][12][13][14] and Monte Carlo simulations. 15 Comparing many classical transport theories in soft and solid state matter based on microscopic-mechanistic concepts with our present understanding of ion transport in potassium channels, the situation is not satisfactory, at least from a theoretical point of view.…”

Upcoming Physics Challenges for Device Modeling

“…Gramicidin A, porins, and potassium channels are the most studied protein channels. Theoretical models for the conduction mechanisms [6], selectivity [7], and current and noise properties [8] are available and provide results in good agreement with experiments. These results suggest that the innovation introduced by ion channels functionalized as biosensors would be the enhanced control of the analyte, i.e., of the substance to be detected, which can be in principle revealed even at molecular concentration.…”

Ion fluxes through nanopores and transmembrane channels

“…There are many different ion channels in living cells. They differ in composition, pore structure, and ion selectivity [2,3]. Thus, a full description of the architecture and operation of ion channels is a very difficult task.…”

“…One approach used extensively over the last few years is all-atom molecular dynamics (MD) simulation. The advantage of atomistic MD is that molecular structures of the pore, ionic species, and water are taken explicitly into account [3,[7][8][9][10][11][12][13][14]. Although this method is very appealing, it remains a huge task to relate the measured observables to the experimental results.…”