D.K. dk at
Tue Jan 1 23:52:07 EST 2002

Tim Davies <daviest at> wrote:
>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
>Tim Davies

I am not an expert in the field, but... I doubt processing power alone
is a limitation. As Artem noted, folding of proteins is aided by
other proteins and such interactions are poorly understood. Also, at 
least some folds, if not most, appear to fold not into global free energy 
minimum. I worked with several proteins that fold spontaneously in 
solution into something that has seemingly nothing to do with their 
native folds.

As for computational power involved, I vaguely remember an article
back from few years ago that illustrates the problem well. There,
a strict calculation of dynamics of hexapeptide in solvent during 10 
microseconds took several months using a bunch of powerful computers. 
In real life proteins consist of roughly 100X more aminoacids and fold
over at least 10,000X longer periods. Power requirements grow
exponentially with increasing number of elements. 


>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> wrote in message
>> news:3C307889.1C6CDF9 at
>> > 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> wrote in message
>> > > news:3C2F97C9.F33EEC26 at
>> > > > 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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