Residue side-chain interactions and backbone conformations altered upon p.R244P mutation. (A) Close-up of Cx47 WT’s R244 interaction with the negatively charged phosphate of the POPC headgroup (left) and close-up of the conformational change induced by the p.R244P mutation (center) and frequency, per simulation, of native contacts (defined as distance <7 Å) formed between the residue side chain at position 244 and charged lipid headgroups. (B) Comparison of secondary structure adopted by the residues in the neighborhood of position 244 across protomers along the MD simulations. Intensity of red indicates the number of protomers out of 18 assuming a β-strand conformation. (C) Differences between WT and p.R244P for electrostatic interaction distances between the indicated salt bridges in the electrostatic network.