2.1 | Effect of a single mutation on conformation, T1109 and T1110
Targets T1110 and T1109 are the wild-type structure of an isocyanide hydratase and that of a one-residue mutant. The experimentalist, Mark Wilson, introduced the one residue mutation, D183→A183 (in the CASP sequence numbering), into the homodimer interface as part of a project exploring enzyme dynamics (10). The consequence is a 20-residue domain swap forming alternative inter-subunit interactions (Figure 1) (11). Twenty-two models (16 distinct) from seven research labs reproduced this swap. The average distance between Cα atoms over the 22 models for the 16 ordered swapped residues in the global LGA model-target superposition (6) is 2.0 Å, whereas the corresponding number for the rest of the models is 30.4 Å. The successful groups all used versions of AF2 with enhanced sampling and include methods that performed well in the single molecule and multimer CASP categories (12, 13). This is the first CASP demonstration that these methods are capable of reproducing such mutation-driven conformational changes. More details of the experimental structures are provided in (14, 15).