Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA. Neale, C., Chakrabarti, N., Pomorski, P., Pai, E., F., & Pomès, R. PLOS Computational Biology, 11(7):e1004303, 2015.
Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA [pdf]Paper  Hydrophobic Gating of Ion Permeation in Magnesium Channel CorA [link]Website  abstract   bibtex   
Ion channels catalyze ionic permeation across membranes via water-filled pores. To under- stand 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 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 con- current with small-amplitude fluctuations 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 con- centration to the onset of ionic conduction.

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