It's biology - so there are exceptions and oddities everywhere. Imagine software that evolved by trial and error rather than being designed - it's not 'clean'.

It's biology - so there are exceptions and oddities everywhere. Imagine software that evolved by trial and error rather than being designed - it's not 'clean'... there are no absolutes. It's well known that codons effect translation rate and translation rate could/can effect the kinetic pathway of folding. When a protein folds ( even away from the ribosome ) it isn't in isolation - it's in a solution - being bombarded by Brownian motion of other molecules. It's amazing you are alive at all really - it also suggests most proteins would need the functional state to be strongly energetically preferred. So there are potentially lots of things beyond just the protein sequence that could be important variables. However some proteins will reversibly fold/unfold in simple solution all day long - so it makes sense to start there.