K(+) and Na(+) conduction in selective and nonselective ion channels via molecular dynamics simulations

Abstract

Generations of scientists have been captivated by ion channels and how they control the workings of the cell by admitting ions from one side of the cell membrane to the other. Elucidating the molecular determinants of ion conduction and selectivity are two of the most fundamental issues in the field of biophysics. Combined with ongoing progress in structural studies, modeling and simulation have been an integral part of the development of the field. As of this writing, the relentless growth in computational power, the development of new algorithms to tackle the so-called rare events, improved force-field parameters, and the concomitant increasing availability of membrane protein structures, allow simulations to contribute even further, providing more-complete models of ion conduction and selectivity in ion channels. In this report, we give an overview of the recent progress made by simulation studies on the understanding of ion permeation in selective and nonselective ion channels.

Figure 1

(A) (Cartoon representation) Na_VAb and KcsA structures. Only two out of the four subunits are shown for simplicity. (Licorice) Selectivity filter. (Green spheres) K⁺ ions. (B) Structure of the selectivity filter of KcsA in high- (PDB:1K4C) and low-K⁺ (PDB:1K4D), Na_VAb (PDB:4EKW), NaK (PDB:3E8H), and an NaK mutant (PDB:4K03). S_IN, S_CEN, and S_HFS indicate possible ion binding sites in the Na⁺ channel, and S1–S4 binding sites in K⁺ channels. To see this figure in color, go online.

Figure 2

Conduction in K⁺ channels and Na⁺/K⁺ nonselective channels. (Square boxes) Binding sites S1–S4. (Yellow circles) Na⁺ ions; (different green shades) K⁺ ions, respectively. The highest energy barriers estimated for each state transition in both directions are given, with the corresponding references. (Transparency) Ions not considered in all the cited references. All the energy barriers refer to state transitions in K⁺ channels except the ones at the bottom of the figure that refer to state transition in a NaK-CNG chimeric channel with only three binding sites. The absence of binding site S1 makes energetically feasible the passage of Na⁺ through S2. To see this figure in color, go online.