Figure 1: Strategy for designing proteins that can switch between different conformations.

A) Left: reaction scheme for a protein (blue) that undergoes a conformational change and can bind an effector (orange) in one (circle) but not in the other conformational state (square). Right: Energy landscape for the system shown on the left. B) Schematic representation of the hinge design approach. Alpha-helices are represented as circles (top view, top) or cylinders (side view, bottom). From left to right: A previously designed repeat protein (gray) serves as the first conformation of the hinge. To generate the second conformation a copy of the repeat protein (green) is moved by shifted alignment along a pivot helix, causing a rotation (top and bottom, indicated by circular arrow) and a translation along the helix axis (bottom). The first 4 helices of the original protein form domain 1 of the hinge, the last 4 helices of the rotated copy form domain 2, and an additional helix is copied over from the original protein to serve as an effector peptide (orange) that can bind to this second conformation of the hinge. Both domains of the hinge are connected into one continuous chain (blue) using fragment-based loop closure, and a single amino acid sequence is designed to be compatible with both conformations. C) Design steps from B illustrated using cartoon representations of an exemplary design trajectory. D) Exemplary design models of a designed hinge protein in state X (left), state Y (center), and in state Y bound to an effector peptide (right). Hinge is shown in blue, peptide in orange.