Subject: Re: CCL:Levinthal's paradox

From: Anita Ilze Zvaigzne <[email-masked]>
Date: Tue, 3 Aug 1999 05:06:28 -0500 (CDT)

RE: Levinthal's Paradox and the Speed of Protein Folding:

    Does this theory take into account that protein folding is not
necessarily an isolated event?  That is, there may be chaperonins
assisting the protein to achieve its final state rapidly -- as opposed to
many years?

Sincerely,
Anita Zvaigzne
=============================================================
On Fri, 30 Jul 1999, Peter Shenkin wrote:

> On Fri, 30 Jul 1999, JATI KASTANJA wrote:
> > does anyone know something about the Levinthal paradox? 
> >...
> Therefore, protein folding must be a kinetically controlled process.
> I.e., proteins fold to the most accessible minimum, rather than the 
> most stable minimum.  In this, protein folding must resemble the
> kinetically controlled reactions of organic (and bio-) chemistry.

---

From: Gerald Loeffler <[email-masked]>
Date: Tue, 03 Aug 1999 14:33:58 +0200

Hi!

> assisting the protein to achieve its final state rapidly -- as opposed to

No, the effect of chaperonins is not considered in Levinthals paradox -
and it need not be, because small proteins _do_ reversibly fold in the
absence of chaperonins (another classic: Anfinsen). First things first -
before worrying about the influence of chaperonins one should try to
understand (from a theoretical perspective) the "pure" protein folding
problem.

Apart from that, I think it's fair to say that the significance of the
Levinthal paradox is now mostly historic. Although science is far from
having solved the protein folding problem, the understanding has
advanced to the extent that we find the idea ridiculous that a protein
needs to exhaustively search phase space in order to find its native
conformation. 

Rather, proteins move from "unfolded" conformations to "folded"
conformations (however one exaclty makes this distinction) via
accessible conformations. These accessible conformations vary between
different folding events, which is why one speaks of "folding funnels"
rather than "folding pathways". Whichever exact path a particular
folding event takes, it is generally assumed that all folding events
eventually lead to an ensemble of conformations close to the global
minimum of free energy of the protein.

Any opposition on this last point?

	cheers,
	gerald

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