The flipping of Phe rings requires that groups surrounding the ring move aside momentarily. The rate of ring flipping can be measured using NMR. You are studying two mutant versions of a protein. In both of the mutants, the proteins have considerable secondary structure, based on circular dichroism studies, and bind the hydrophobic dye ANS, indicating the formation of the hydrophobic core of the protein. However, in one of the mutants (mutant A), the rate of Phe ring flipping is much higher than in the other (mutant B). A researcher suggests that one of these mutants completes the folding process to form a misfolded protein, much like a prion, whereas the other is stuck at some point on the folding pathway.
A. Which mutant forms a misfolded structure? Explain your reasoning.
B. Where along the folding pathway is the other mutant stuck? Again, explain your reasoning.