Not a biologist but I keep thinking about this folding path question — probably obvious, just can't shake it
Background first so you know where this is coming from — I'm not in the field at all, I just read a lot and got stuck on something I can't find addressed anywhere. Happy to be told it's already solved.
The proteins that won't classify cleanly no matter how much data you throw at them — the intrinsically disordered ones. The ones that just won't settle.
My question is whether we're looking at the final shape or the path that got it there.
Because if two proteins end up at roughly the same final structure but got there through different folding sequences, the internal contact points would be different. Parts of the chain that are far apart in sequence but end up sitting next to each other in the finished fold — those bridges only exist because of the specific path it took. Different path, different bridges, even if the outside looks similar.
So my question is basically: are those hidden contact points being tracked and compared between the disordered cases and the ones that resolve cleanly? Because if the disordered ones are arriving at their weird ambiguous state via a different pathway, maybe the bridge pattern is the variable nobody's looking at yet.
Probably already accounted for somewhere and I just haven't found it. What am I missing?