"Pedro Mendes" <mendes at vt.edu> wrote in message
news:93cmcd$fji$1 at solaris.cc.vt.edu...
> Mike Cantor wrote:
>> > I am currently worked on the section about rate-equation based kinetic
> > simulations, in particular those that game out of the Garfinkel lab in
> > the early 80s by people like Michael Kohn and Murray Achs. These seam
> > to be the only pathway-level models I have come across at the level of
> > resolution of kinetic simulation.
>> Oh, but there are a lot more. Just as an example, I got these out of my
> bibliographic database:
>> - Schuster, R. and H. G. Holzhutter (1995). "Use of mathematical models
for
> predicting the metabolic effect of large-scale enzyme activity
alterations.
> Application to enzyme deficiencies of red blood cells." Eur. J. Biochem.
> 229(2): 403-418.
>> - Aksenov, S. V., E. A. Krasavin, et al. (1997). "Mathematical model of
the
> SOS response regulation of an excision repair deficient mutant of
> Escherichia coli after ultraviolet light irradiation." J. Theor. Biol.
186:
> 251-260.
>> The work that came out of Garfinkel's lab was very important. It was a
> pioneering effort that at least put this type of approach on the map early
> on (I would even reccomend that you read the very early papers by Chance
> and Hess and Garfinkel, from the late 50s and early 60s). However, I was
> much more inspired by the thinking of Kacser and Burns and by a 1986 book
> by Hayashi and Sakamoto, "Dynamic analysis of enzyme systems. An
> introduction".
>
Someone who is often overlooked in the BG (Before gemonics) simulation era
is David Park. He developed a simulation packaged called (I think) Metasim,
it wasn't so much the package as the algorithm he implemented. He has a
paper in J theor biol, 1974 where he describes in some depth how to
dynamically partition reactions which are fast and can be treated as if they
are in quasi-steady state and those which are not. During the simulation
these two groups change composition as fast reactions become slow and slow
reactions become fast. Quite impressive and as far as I know it's never been
implemented since.The advantage of this is that for large models simulations
time can be greatly reduced and numerical integration is easier.
> > 2. The eighties and early nineties saw a proliferation of software
> > packages for metabolic simulation, yet these seam to nearly outnumber
> > the number of models actually constructed at the pathway level. Why is
> > this? Who are the primary users of, for instance, SCAMP, Gepasi,
> > Kinsim, DBsolve, SCoP, etc.
>> I don't think it is true that the number of papers on simulators is larger
> than on simulations. For example, my own program Gepasi has a list of
> around 50 papers that have used it for research. You can see this list at
>http://www.gepasi.org (follow the link "Gepasi in research".) The same
> happens with Scamp, although I don't think that Herbert has compiled such
a
> list.
>I agree with Pedro, last time I checked there were just over 50 papers which
used Scamp. There's another paper this month in Biochemical Journal. So
biochemical simulation is certainly not dead. Also there has been a marked
interest in N American in this field since the human genome was sequenced
and there is now an 'alternative' community which is starting to do such
modelling although its very early days for them yet. Note that Leroy Hood
has set up an entire institite devoted to computational biology.
Herbert Sauro
