Extended Data Fig. 4: Backbone and hydrogen-bond network permutations.

a, On a 2 + 2 backbone (left), two loops were designed to connect the four helices into a single monomer in two different ways (middle), after which four different cut points were introduced to generate four possible backbone-permuted heterodimers of a single helix and a three helix bundle (3 + 1 heterodimers, right). For example, 2:134 refers to a heterodimer in which the original helix 2 is a single helix, and helices 1, 3 and 4 were connected into a three-helix bundle. b, Hydrogen-bond network permutation. Each unique network was assigned a letter (networks ‘A’ and ‘B’ in this case), with the hydrophobic packing assigned X. The backbone on the left reads ‘ABXB’; its first heptad accommodates network A, its second and fourth heptad accommodate network B, and its third heptad accommodates hydrophobic packing only (X).