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.
- Bakker, B. M., P. A. M. Michels, et al. (1997). Glycolysis in bloodstream
form Trypanosoma brucei can be understood in terms of the kinetics of the
glycolytic enzymes." J. Biol. Chem. 272, 3207-3215.
- Holzhütter, H. G., A. Schwendel, et al. (1993). "Estimation of
steady-state flux rates in metabolic systems by computer simulations of
radioactive tracer experiments." Comput. Appl. Biosci. 9(5): 573-580.
- Wright & Kelly (1981) "Kinetic models of metabolism in intact cells,
tissues and organisms" Curr. Top. Cell. Reg. 19, 103-158
- Centelles, Cascante et al (1992) "A model for adenosine transport and
metabolism" Biochem. J. 287, 461-472
- Wright and Albe (1994) "Carbohydrate metabolism in Dictyostelium
discoideum: I. Model construction", J. Theor. Biol. 169, 231-241
- Turner et al. (1974) "Simulation of biogenic amine metabolism in the
brain" Biochem. J. 144, 353-360
But a careful bibliographic search will reveal a lot more.
> 1. I am curious to read what people think of as the legacy of this
> work. How did it influence your work and what do you see as its most
> significant contributions, biologically or computationally?
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".
> 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.
> Thanks again for all your help. I am trying as best as I can to present
> the work of this community to the bioinformatics world in this review,
> so if anyone wants a particular piece of information to get reported,
> feel free to drop me a line.
Incidentally, I think that the bioinformatics community is (or should be)
somewhat well aware of this area. If nothing else, most modern simulators
(eg Scamp, Gepasi, MeraModel, MIST) were published in the journal that is
now called Bioinformatics! But I guess that a review will not harm anyone
here, as long as you manage to portrait the field with accuracy.
By the way, you may be interested in reading a litle review that I wrote
back in 1996. It is centered mostly on the computational techniques rather
than the models themselves, but it may still be useful. You can find it
online at http://gepasi.dbs.aber.ac.uk/pedro/btk96rev.html
