Homology model of Cx47, simulated in a POPC bilayer membrane environment. (A) An extracellular view of the Cx47 WT hemichannel homology model serving as the starting model for all MD simulations. (B) A lateral, in-membrane view, with alignment to the pore radius profile as determined by the HOLE program. Purple licorice-style side chains are laterally aligned to their corresponding labels on the graph (Gly40 is pore-lining and so is obscured). (C) Chain A, displaying the side chains of notable residues (purple: electrostatic cluster; yellow: hydrophobic core; red; N-terminal neighboring, buried charged residues. (D) Close-up of interprotomeric (left), pore-lining intraprotomeric (middle), and lipid-facing intraprotomeric salt bridges (right) comprising the electrostatic side-chain cluster. Notable residues are labeled in A, B, and D.