Fig. 2.

Native-state residual frustration and two-state behavior of the designed double mutant Y55R, Y56N. (A) Local frustration is depicted on the native IM7 wild-type structure (from Protein Data Bank ID code 1AYI). A large cluster of minimally frustrated contacts (green) defines the core of the protein, but some highly frustrated contacts (F_ij < −1) surround the core (indicated in red). (B) Native contacts of wild-type IM7 in the native (upper-left) and intermediate (lower-right) states. Highly frustrated contacts (red) are primarily local compared with all contacts present in the native state. Within region III (blue box), multiple frustrated contacts remain unformed in the intermediate. (C) Free energy (in units of ε) of the IM7 designed mutant at T̄ = 1.0 as a function of Q_W and rmsd. The minima correspond well to the unfolded (U) and native (N) states of the wild-type protein.