Fig. 1.

(A) Schematic of a hydrophobic gate in an ion channel. A hydrophobic gate region (dashed line) can spontaneously dewet to form a dry (i.e., vapor) state and functionally close the channel. Widening of the gate leads to wetting (i.e., hydration) of the region and a functionally open state. Water is represented by the pale blue background shading; ions, by red and blue spheres. (B) Pie chart summarizing the ∼200 channel dataset that forms the basis of the present study. The channels are grouped into 9 broad families: cys-loop receptors, ionotropic glutamate receptors, purinergic receptors, TRP channels, K⁺ channels (2TM, 4TM, and 6TM), other members of the voltage-gated ion channel (VGIC) superfamily, other cation channels, and other anion channels. (C) Representation of a typical simulation system used in this study. Shown is the TRPV4 channel in a phospholipid (gray) bilayer. Water molecules and ions are present but omitted for clarity.