<p>A. NMR structure of hERG S4–S5 linker, from Asp540 to Leu550, superimposed on to the hERG homology model generated using Kv1.2 crystal structure <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031640#pone.0031640-Long2" target="_blank">[36]</a> as the template. Only one subunit is shown here for clarity. Each segment is labelled accordingly from S4 to S6. Residues from Asp540–Leue550 are coloured-coded based on their sidechains as in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031640#pone-0031640-g001" target="_blank">Fig. 1C</a>. View (ii) shows the proximity of the S4–S5 linker to the residues from the S6 in the open state. B. Surface representation of residues Asp540–Phe550. Views shown are: (i) and (ii) S4–S5 linker parallel to the membrane with S4 and S5 helices at either end; (iii) membrane buried and (iv) solvent exposed surfaces. C. The surface electrostatic potential was calculated using APBS software <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031640#pone.0031640-Baker1" target="_blank">[50]</a>. The membrane-buried surface (i) is neutral whereas the solvent exposed surface (ii) has an overall small negative charge.</p