PTx2–VSD IV binding interfaces in the top scoring Rosetta structural models. (A and B) Panel A shows PTx2-deactivated VSD IV, and panel B shows PTx2 - activated VSD IV interactions. (i) Front view of the complex highlighting interactions with the VSD that comprise the polar binding interface; R1 highlights the position of the first gating charge. (ii) Back view of the complex highlighting interactions with the VSD that comprise the hydrophobic or membrane-interacting interface. (iii) Detailed interactions at the polar interface; yellow dashed lines indicate hydrogen bonds. (iv) Detailed interactions at the hydrophobic interface. The membrane is represented as a gray box, with the extracellular-facing side labeled as “EX.”