Artem Evdokimov AEVDOKIMOZ at cinci.rr.com
Mon Dec 31 14:26:49 EST 2001

Well it's easier to ask what do we know in this case, than what we do not.
Even if we think of solving the folding problem by sheer brute force - i.e.
by computing every interaction between the polypeptide chain, solvent, ions,
etc. we still do not exactly know how to describe individual interactions.
The best tool to do that is, undoubtedly, quantum mechanics because
'molecular dynamics' is, essentially, utter disaster - at least until some
clever postdoc discovers a way to describe the interatomic interactions that
does not involve rubber bands and bouncy balls on strings.
Even if there were computers big enough to calculate all the necessary
parameters we are still left with a question of how deep does our QM
calculation has to be in order to succeed. It has been demonstrated many
times that if one does not use an orbital model that is complete enough or
if one does not use total correlation, etc. then the results of QM
calculations are dubious. It has been shown that in many cases DFT (density
functional theory) can save one a lot of processing time but even DFT
calculations for something as big as even a modest peptide are, at present,
impossible. If you add solvent atoms and the need to compute things until
they converge (which, in case of folding can be very long in computational
terms) then the problem becomes truly scary.
Then, there's a question of how does the folding of the polypeptide depend
on the ribosome from which the nascent peptide chain emerges, and on the
chaperones and other cellular components. Yes, there are proteins which are
known to fold by themselves, but many (I am inclined to guess that most)
proteins aren't that easy.

I am sure that if you ask a number of scientists in the field there will be
conflicting opinions, deviating in both the optimistic and the pessimistic
direction from mine. However, I am equally sure that a number of people will
express similar if not identical (rather pessimistic) outlook on the current
situation in folding simulaitons.



"Tim Davies" <daviest at shaw.ca> wrote in message
news:3C307889.1C6CDF9 at shaw.ca...
> thanks for the information. i had no idea that the math was not
> understood.
> What information could be missing?
> thanks
> tim
> Artem Evdokimov wrote:
> >
> > No. The problem isn't just mathematical - it is fundamental - the
> > does not have all the relevant information, so the folding models that
> > build are incomplete.
> >
> > A.G.E.
> >
> > "Tim Davies" <daviest at shaw.ca> wrote in message
> > news:3C2F97C9.F33EEC26 at shaw.ca...
> > > I am wondering if there are any known sets of equations which
> > > predict folding and resulting structure. The calculation complexity is
> > > not relevant just the interest to learn if there is in fact a set of
> > > math which describes the phenomenon accurately
> > > Thanks
> > > Tim Davies

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