Molecular interactions for S209 and V215 from the KCNQ1 homology model. Polar S209 moves to a hydrophobic pocket in the open state. (A) Close-up view of the residues within van der Waals contact of S209 in the KCNQ1 closed- and (B) open-state models. S209 from the green subunit is in space fill. Residues determined to have side chains in Van der Waals contact (see Materials and methods) with the side chain of S209 are labeled and have side chains shown in bonds-only mode. (C and D) The KCNQ1 models predict that V215M can be accommodated in the closed state but perturbs the open state. The V215M mutation was made in the KCNQ1 homology models, and the WT and mutant channel were then subjected to side chain repacking and gradient energy minimization. The WT channel is in blue, and V215M is in orange. The amino acids at 215 as well as A223, I227, I230, and L233 are shown in bonds-only mode.