Paper Citing NAMD - Abstract
Furini, Simone; Beckstein, Oliver; Domene, Carmen
Permeation of water through the KcsA K+ channel
PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS, 74:437-448, FEB 1 2009
Previous studies have reported that the KcsA potassium channel has an osmotic permeability coefficient of 4.8 X 10(-12) cm(3)/s, giving it a Significantly higher osmotic permeability coefficient than that of some membrane channels specialized in water transport. This high osmotic permeability is proposed to occur when the channel is depleted of potassium ions, the presence of which slow down the water permeation process. The atomic structure of the potassium-depleted KcsA channel and the mechanisms of water permeation have not been well characterized so far. Here, all-atom molecular dynamics simulations, in conjunction with an umbrella sampling strategy and a nonequilibrium approach to simulate pressure gradients are employed to illustrate the permeation of water in the absence of ions through the KcsA K+ channel. Equilibrium molecular dynamics simulations (95 ns combined total length) identified a possible structure of the potassium-depleted KcsA channel, and umbrella sampling calculations (160 ns combined total length) revealed that this structure is not permeable by water molecules moving along the channel axis. The simulation of a pressure gradient across the channel (30 ns combined total length) identified an alternative permeation pathway with a computed osmotic permeability of similar to(2.7 +/- 0.9) X 10(-13) cm(3)/s. Water fluxes along this pathway did not proceed through collective water motions or transitions to vapor state. All of the major results of this study were robust against variations in a wide set of simulation parameters (force field, water model, membrane model, and channel conformation).
