 The hydrophobic gating model suggests that ion permeation through pores is inhibited by the hydrophobicity of the pore walls, rather than a physical occlusion of the pore. This model has been studied extensively in potassium channels, but its effects on the function and structure of these channels remain unclear. In this study, molecular dynamic simulations were used to investigate the effect of hydrophobic gating on potassium channels. It was found that the activity of potassium channels is strongly correlated with the hydration level of their cavities, suggesting that insufficient hydration is a major obstacle to ion permeation. Furthermore, enforcing dehydration of the cavity caused the channels to transition from one state to another, indicating that the dewetting of the cavity is a crucial step in the gating process of potassium channels. These results suggest that the hydrophobic gating mechanism is responsible for the regulation of potassium channel activity and structure. This article was authored by Ruoshu Jiu and Bert Eldergrut. We are article.tv, links in the description below.