Fig. 2.

Misfolded structures and their contact maps. (Left) A domain-swapped misfolded structure from simulated annealing simulations of the fused dimer SH3-SH3. (Right) A misfolded structure with a significant amount of self-recognition contacts from simulations of the fused dimer I27-I27. The different levels of frustration in the tertiary contacts as determined by the frustratometer analysis (28) are illustrated in the structures. In the structures, the two domains are in blue and yellow color, respectively. Minimally frustrated interactions are shown in green lines, and frustrated interactions are in red. The swapped contacts formed at the domain interface of SH3-SH3 are minimally frustrated, as expected from the principle of minimal frustration for native contacts. The self-recognition contacts formed at the domain interface of I27-I27 are also minimally frustrated, indicating that these contacts are stronger than random contacts. Within the set of four contact maps for each fused dimer, the lower left and upper right contact maps are for each domain, respectively. Formed native contacts are represented by black dots, formed nonnative contacts are in red, and the native contacts that are not formed are in yellow. The upper left contact map is the interdomain contact map. Black dots stand for formed swapped contacts. Red dots represent other types of interdomain contacts. In the case of I27-I27, we observe a different type of contact, the self-recognition contacts (in red), along the diagonal of the map. The lower left contact map is a summary contact map showing the total number of occurrences of each formed contact from the end structures of 40 annealing simulations. For SH3-SH3, the swapped contacts that are formed between the residues near the linker position appear more frequently than those that are more distantly connected through the sequence. For I27-I27, the self-recognition contacts formed between residue indexes 56 and 61 (HILILH) appear in almost all of the simulations.