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So, this morning I was thinking about this whole foldit thing.....there's a lot of assumptions before we step into the folding process, I think.
One of them is the fact that a protein folds in a way that takes the least amount of energy.

Even though that's a very plausible theory, it made me wonder the following (and here's where I need anyone to step in with additional thoughts, even when they contradict my thoughts...I'm just curious):

ahem....before the folding process, the primary structure of a protein is known, then it is assumed to be one long string of amino acids, and it is folded in every possible way by computers and humans to reach the lowest-energy state.

Now, what I was thinking is this: when a protein is synthesized, it is NOT one long string of amino acids....when the first part is made, it probably started folding far before the last part is attached?!
The tertiary structure will probably not reach the assumed "least energy state", as strong bonds will already have formed, preventing different shaping.

Do i make any sense...ANY?...Bueller, Bueller?

Ok, I'm out, just curious about your thoughts...

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I believe you are correct regarding when the folding takes place.

In fact, this new "catalytic constraint" thing in the view menu appears to be exactly that...I looked up the term after the request for its definition was summarily dismissed by the admin as too technical and found that it means that a strand of DNA acts to govern the folding process...this is the "Catalytic Constraint"

As I recall in looking up "Chaperones", the graphic used showed the chaperone nearby the emerging protein as it was being formed...

Good thinking

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Thank you, thank you, thank you....

Thank you for giving me names and words to look up, so I'm able to look into my thoughts further.

I knew that if my thoughts would make any sense, I wouldn't be the first one to think it up, lol.

So again, thanks, you opened up a new part of the folding world to me!

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yes indeed you might be

yes indeed you might be interested in looking up the word chaperones, which basically are proteins that help other proteins to fold, (for instance by helping them to do things they would not be able to do alone because the energy barrier would be too big).

And you are right that proteins can start to fold when they are being formed. If you would unroll a protein and then let it fold, not all proteins would fall back in their original or their right structure. That's when chaperones might come in handy.

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Not so weird...

There is a great animation piece on Youtube:


showing building a protein, animo acid by amino acid. It doesn't deal with folding at all, but it begs the question of what happens while the chain is being formed. From what I've learned, the protein begins to form immediately and if it isn't exactly formed right it can pull itself apart and reform into a better situation (whatever that means) as more of the chain is added.

So that would imply that the geometry of the protein fold is dictated in part by the sequence of the chain and in part by an amino acid's sidechain neighbors, as its being folded.

Question: Could there be more than one correct fold? I would guess, yes.

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No Prob

anytime Nicky I enjoy talking science, even in the dark ;)

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Thanks for the contributions

Thanks for the contributions all.

The way we use the term "catalytic constraint" does not have to do with chaperones or the folding process. As far as Foldit is concerned, folding during the protein's synthesis (translation) does not occur. Chaperones typically only speed up the folding process in nature.

Just to correct a small mistake above: the definition of catalytic constraints was not "dismissed by the admin as too technical". I should know as I was the admin referred to. I said it's part of an upcoming feature that was not meant to be in the current update. For now, it is there as an accident, and it will be explained only when the corresponding Foldit feature is released.

Nicky, I will alert a biochemist as to this topic so he can provide a more accurate answer than I have given.

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beta_helix writes:
"Actually, there have been recent studies where a fully folded protein
was denatured and then starting from this denatured state it folded
back into the same native conformation!"

So there is indication that our assumptions (i.e. no folding during the protein's synthesis) are true for at least some proteins, although it is difficult to say for how many. Further validation of the idea comes from the fact that Rosetta and Foldit, which both incorporate this assumption, often find solutions very close to the native form. You cannot regard the assumption as absolutely true, but then again this is research; we are doing it precisely because we don't know the answers, and yours is an interesting thought.

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Thanks again!

...for all the additional thoughts and the youtube movie (even though it was no longer available, I'm afraid..)

admin, after learning the terms "catalytic constraint" and "chaperones", I have only read a small part of everything I want and need to read, but there's something I'd like to add to my earlier comment (something I said out loud in chat, and which actually was the core of my thoughts in the first place);

if a protein would start to fold immediately after translation, wouldn't that mean we should start at one end of the protein and forces of nature (ie hydrogen bonds) will be locking up the folding process on part of the protein once a certain energy threshold is reached?

Oh, by the way, I do understand you need to make assumptions to get closer to an answer, there's nothing wrong with that. As far as I'm concerned, foldit acts like a mathematical model. No need to complicate it by making further assumptions, but it does make you look at things in different ways...it raises questions, which is a good thing, I think.

Anyway, thanks again for all the responses!

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See R@h forums

This subject was discussed some time ago in the Rosetta@home forums: you might find it interesting.


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Yes, it is indeed

Yes, it is indeed interesting to learn about other peoples thought on the matter, thanks for linking to that thread, babe!


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