Talk:Levinthal's paradox

Added Paradox Qualification
Because the "paradoxical" aspect of Levinithal's paradox evades many of us, I have qualified it appropriately. —Preceding unsigned comment added by 76.19.164.81 (talk) 00:01, 1 October 2010 (UTC)

Removed section
I have removed the following section. As it is now, it is completely incomprehensible, even to someone working in a related field:

"It has been argued that the paradox can be settled if one views each atom as independently computing in its neighbourhood; that is, the atoms compute in parallel whereas the theoretical calculation assumes a sequential search."

Kjaergaard 05:19, 12 April 2006 (UTC)

Hoax box
I removed hoax box. This is a genuine article, even though it might need to be rephrased... Kjaergaard 05:29, 12 April 2006 (UTC)
 * The article makes no sense at all. Molecules don't perform searches, or calculate anything. Peter Grey 05:31, 12 April 2006 (UTC)
 * No they don't calculate anything, but to some extent it is true, that proteins search/sample conformation space during folding.... Kjaergaard 05:34, 12 April 2006 (UTC)
 * It seems to be describing what one would intuitively expect any molecule to do. Perhaps the article should indicate what this behaviour is supposed to contrast with. Peter Grey 15:53, 12 April 2006 (UTC)
 * The references seem to be suggesting that the phenomenon is not an actual paradox, but "paradox" is simply a metaphor for contrasting a computationally intensive search with the behaviour of molecules under electromagnetic forces. Of course, the molecule does not have a conscious goal, and is not conducting a random search, so this is really a comparison of completely unrelated quantities.  Or is there something missing from the story? Peter Grey 07:01, 13 April 2006 (UTC)
 * Regarding the use of the word paradox, this particular subject has been known as Levinthal's paradox, and I guess we just have to stick with that name regardsless of whether we think it is a paradox or not. I think what might be missing is the historical dimension. The original ref. is from '69 and that was a time when a lot less was known about the nature of proteins. I think maybe from the general perception of how molecules behaved in '69, a random search was maybe not that silly proposition. Kjaergaard 16:11, 13 April 2006 (UTC)
 * Not true. Levinthal was well aware that they did not undergo a random search, since it was already known that proteins fold quickly.  The question was how.  he just demonstrated formally that folding couldn't be random.  User:W Little

Puzzle
Levinthals paradox is not a puzzle. It is a thought experiment that leads to the assumption that proteins must fold via defined folding pathways. —The preceding unsigned comment was added by 129.67.21.28 (talk • contribs) 11:12, 19 May 2007

Call me slow by all means, but ...
what is the _paradox_? Midgley (talk) 15:44, 11 January 2008 (UTC)

the paradox is that if a protein would fold completly randomly, and try every possible position for a given amino acid, it would take many many years before it will find his correct fold. We know that a protein folds in not much more than a couple of seconds, so the folding proces can't be randomly. that is the paradox. Scientist can't figure out why a given AA sequens will become a given proteinstructure, and nature hasn't any problem at all with it —Preceding unsigned comment added by 81.246.152.91 (talk) 19:56, 29 January 2008 (UTC)

I AGREE There is no paradox. I have updated the article to reflect this fact. —Preceding unsigned comment added by 76.19.164.81 (talk) 23:59, 30 September 2010 (UTC)

Protein Folding
Maybe I missed something, but my understanding is that proteins are synthesized one residue at a time and the folding occurs as they are synthesized. Chaparones are also there to facilitate the process. This reduces the degrees of freedom down to more than reasonable levels. I am pretty sure that no protein is synthesized as a long chain of unfolded amino acid residues until somebody says "go" and it roots around in conformational space to find the "right" conformation. In any case, there are so many local energy minima that most proteins would just clump into some kind of useless piece of garbage and be chewed up.Desoto10 (talk) 05:48, 31 May 2009 (UTC)
 * Apparently Levinthal did think of that Shyamal (talk) 09:12, 13 June 2009 (UTC)

Redirection
There appear to be citation issues, but as far as is known the topic is well known and there appears to be little reason for redirecting to the author. Rolling the edit back. Shyamal (talk) 07:27, 13 June 2009 (UTC)

Should this parenthetical be removed from atop the article?
"(often incorrectly cited as a 1968 paper)" Seems like to much of an obscure point, especially to be placed near the top of an article. Bob Enyart, Denver KGOV radio host (talk) 00:13, 11 December 2016 (UTC)
 * I think it should be included. For example, I noted down from a book that it was suggested in 1968. But the wikipedia article here mentions 1969, so now I am not sure which variant is correct. Perhaps a short history-section on the top should mention this. 2A02:8388:1640:9200:610B:3D3A:CFF:615 (talk) 02:50, 10 March 2018 (UTC)

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Random search
Regarding the alteration from "algorithmic search" to "random search" in the lead - I suspect that "random search" is almost an oxymoron - "search" involves going through every element of the total conformation space. Levinthal (1968) clearly states the possibility that local solutions are likely grown gradually to accomodate the full protein - "One possible sequential process which might lead a protein to land in a particular state, is the growth of the peptide chain on the ribosome, starting with the amino terminal end and proceeding to the carboxy terminus. Although one could imagine a protein folding as it grows, and thus attaining a particular metastable state, this is clearly not a necessary condition for correct folding, at least for those proteins which have been shown to be reversibly denaturable. However, the fact that folding on the ribosomes is not necessary for the establishment of structure, does not imply that any theory invoking a pathway of folding can be eliminated" - and the 1969 work states "Well, let us consider the various parameters involved. How accurately must we know the bond angles to be able to estimate these energies? Even if we knew these angles to better than a tenth of a radian, there would be 10300 possible configurations in our theoretical protein. In nature, proteins apparently do not sample all of these possible configurations since they fold in a few seconds, and even postulating a minimum time for going from one conformation to another, the proteins would have time to try on the order of 108 different conformations at most before reaching their final state. We feel that protein folding is speeded and guided by the rapid formation of local interactions which then determine the further folding of the peptide. This suggests local amino acid sequences which form stable interactions and serve as nucleation points in the folding process." - I think the use of random is particularly problematic and non-factual as a random approach to finding a minimum conformation was never proposed by Levinthal. Shyamal (talk) 02:59, 8 May 2024 (UTC)


 * Levinthal was not genuinely proposing that the random approach was true. The random sampling (I agree "search" is a bad word to use) was one of the supposed ideas at the time, and was what he was arguing against. The point is to suggest a methodical approach to protein folding. Niashervin (talk) 03:57, 8 May 2024 (UTC)
 * "Random sampling" is even worse of an interpretation - it was not a statistical experiment - you can actually read carefully what he says "for going from one conformation to another", he is implicitly suggesting either breadth-first or depth-first tree traversal. In order to identify a minimum energy - an exhaustive analysis of all conformations would be needed in that thought experiment - that is hardly what anyone would call "random sampling". Shyamal (talk) 06:05, 8 May 2024 (UTC)
 * Well, you wouldn't necessarily have to go through *all* combinations to find the correct one, so it's not totally devoid of any statistics. But, this is all beside the point. I updated the opening paragraph. Feel free to make suggestions for wording. Niashervin (talk) 21:45, 8 May 2024 (UTC)
 * "you wouldn't necessarily have to " - let us not confuse our opinions with the actual topic here - Levinthal saw the contradiction in the thought experiment versus reality - of course one can interpolate an energy surface by statistical sampling and find local or global minima by better approaches - and Levinthal was aware of that. Shyamal (talk) 02:09, 9 May 2024 (UTC)