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).