structure

Artem Evdokimov AEVDOKIMOZ at cinci.rr.com
Mon Dec 31 22:02:44 EST 2001


QM total correlation with an expanded basis set on a protein+solvent
requires astronomical amount of calculations. It's not likely to happen
within reasonable future, nope, nope.

Solving problems by brute force works only to some extent. Sooner or later
the numbers win simply because the density of information, even in the ideal
case of 'quantum computers' and such is still less or equal (so far, MUCH
LESS) to the density of the information-bearing matrix, be it transistor
states or spin states of nuclei. Nature has no such limitaitons because it
can try gadzillions of molecules for millions of years, in order to achieve
the desired effect. In essence, predicting protein folding by brute force is
likely to be computationally equivalent to simulating natural molecular
evolution.

Ergo, an elegant solution is needed - not more power but wiser application
of it. It is likely that such elegant method will still require enormous
(but manageable) amounts of computation.

The interest in the resulting structures is quite simple to explain - people
want to know how proteins look like, in order to understand how proteins
work, and all the ensuing benefits (drug design, molecular engineering and
so forth).

Happy new year.

A.G.E.
"Tim Davies" <daviest at shaw.ca> wrote in message
news:3C310CE2.1BBD714 at shaw.ca...
> My thanks for the reply:
> The problem would seem to be the computational limitations. In both of
> the cases that you feel are satisfactory ( the qm and orbital (which
> sound similar)) have very large computational requirements. This is
> similar to the solution to the elastic wave equation in 10 or 10 k
> velocity layers in the case of sound (it cant be done yet in its
> complete form). I cant help but wonder if you did have a box that would
> do 100 or 200 trillion instructions per sec then would it be possible?.
> only if there is something to model can this be determined. I think its
> a problem worth looking into. There seems to be a lot of interest in the
> resulting structures. Im not sure why there is interest other than it
> saves time, but the computational complexity is most interesting to me
> Thanks
> Tim Davies
>
> Artem Evdokimov wrote:
> >
> > 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.
> >
> > Cheers,
> >
> > A.G.E.
> >
> > "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
> > science
> > > > does not have all the relevant information, so the folding models
that
> > we
> > > > 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
> > completely
> > > > > 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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