Ion channels catalyze ionic permeation across membranes via water-filled pores.To understand how changes in intracellular magnesium concentration regulate the influx of Mg2+ into cells, we examine early events in the relaxation of Mg2+ channel CorA toward its open state using massively-repeated molecular dynamics simulations conducted either with read more or without regulatory ions.The pore of CorA contains a 2-nm-long hydrophobic bottleneck which remained dehydrated in most simulations.However, rapid hydration or "wetting" events concurrent with small-amplitude fluctuations Airliner Model Kits in pore diameter occurred spontaneously and reversibly.
In the absence of regulatory ions, wetting transitions are more likely and include a wet state that is significantly more stable and more hydrated.The free energy profile for Mg2+ permeation presents a barrier whose magnitude is anticorrelated to pore diameter and the extent of hydrophobic hydration.These findings support an allosteric mechanism whereby wetting of a hydrophobic gate couples changes in intracellular magnesium concentration to the onset of ionic conduction.