FIGURE 1.

Steps in applying mPROSS to the Kv channel. (a) Scheme of the mPROSS algorithm. mPROSS starts with a phylogenetic analysis of homologs of the target protein and inserts the protein into a virtual membrane. The structure is minimized and subjected to combinatorial design calculations, generating designs with different mutational loads for experimental analysis. (b) Overview of the paddle chimera structure, including the β‐2 soluble subunits responsible for attenuating channel dynamics (PDB entry: 2R9R). The selectivity filter is indicated in orange, and the voltage sensor is in red. The left‐hand side shows the tetrameric arrangement of the channel looking from the extracellular domain toward the fourfold symmetry axis of the channel. Pink spheres indicate K⁺ ions. The right‐hand side shows a side view of one protomer, and a single β‐2 subunit is shown as a molecular surface.