2.6 | RNA Folding intermediate, R1138
Ewan McRae and Ebbe Andersen supplied two designed (‘origami’) RNA structures as CASP targets (15). One of these, R1138, was found to have two conformations (now PDB 7PTK and 7PTL, Figure 4): these represent the mature form, and an intermediate form present in solution for approximately the first 8 to 10 hours after transcription. Participants were asked to predict both conformations within the set of five models allowed for a target. This is a large molecule (720 bases). There are quite accurate models of the mature form (TM ~0.8), but not of the intermediate. However, inspection of the structure suggests the free energy of the intermediate is likely substantially higher than the mature form compared to the free energy spread in the other ensemble targets and to situations explored in benchmarking studies (17-20), so it is unclear whether the enhanced sampling methods used there and on the other targets could be effective.