In <9407080642.ZM25108 at model.phr.utexas.edu>
David G. Rhodes writes:
>I have what may be a naive question.
>Are these discussions concerned with "real" folding (i.e. as the protein is
>synthesized) or "experimental" folding (i.e. renaturation). There are
>parts of the discussion that suggest either possibility, and it will make a
>big difference. ... Another way of saying that the choice of possible
>pathways is quite limited, so the distinction under discussion becomes
>somewhat less clear. (no? yes?)
Yes, it is the BIG difference. In "real" conditions synthesis and folding
are two competitive processes occuring in the same, real time - the part
of protein chain which had already been synthesized folds while the rest
of the chain is still to come into existence. It may lead to the structures
which when synthesis is finished are NOT in thermodynamic equilibrium -
they have an intrinsic physical instability; we think that the proteins
with short half-time "work" in states far from thermodynamic equilibrium
(cf. Klonowska and Klonowski, BioSystems 21 (1988) 135-139).
S.Ji calls such protein structures "Klonowski-Klonowska Conformons"
(cf. 'Molecular Theories of Cell Life and Death', Ji S., Ed. Rutgers UPress,
1991, p.42-43)
So, one can say that biosynthesis of such proteins is kinetically controlled,
but for other proteins thermodynamics may prevail over kinetics - it depends
very much on the protein's primary structure.
During renaturation the whole chain already exists and the final structure
is most probably thermodynamically controlled. For some proteins it may be
the same or a very similar structure as a 'native' one. For these which form
"Klonowski-Klonowska conformons" it will be a very 'non-native' structure,
these protein would never be able to get renaturated.
BTW, if you know about proteins which have resisted all efforts of being
renaturated, as well as about proteins with short life-time (say less than
30 min.) please e-mail me the information. Thank you.
Dr. W. (Vladimir) Klonowski
res4010 at husky1.stmarys.ca
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