Residues selected as informative features by wrapper and mapped onto VKC structures. A. Schematic structure of the VKCs. Six transmembranehelices, labeled S1 through S6, traverse the plasma membrane. The N-terminus and C-terminus are both cytoplasmic. The loop connecting S5 and S6 folds into the channel to form the ion-selective pore. The S4 region, in which every third residue is positively charged, is the central voltage-sensing element of the VKC. The six residues selected by the wrapper algorithm are approximately mapped onto the schematic diagram (black dots). Four highly conserved acidic residues are indicated by black stars. The numbers assigned to each marked residue are positions within the dataset alignment, not positions in any actual VKC protein sequence.B. Schematic end-on view of helices S1, S2 and S3 with the radial positions of conserved acidic residues (numbered in black) and four of the selected residues (numbered in red) indicated. Residue 117, 125, 135 and 154 are each exactly two residues away from a highly conserved negatively charged residue, 115, 127, 137 and 152 respectively.