Petr Kuzmic <pkuzmic at biokin.com> wrote in message
news:399F568A.7D2A0EED at biokin.com...
>> I would like to ask if anybody remembers the work of David Garfinkel in
> computer simulation of metabolic pathways in the 1960's. This, to me
> anyway, was a very serious attempt at applying computational techniques
> to biochemical metabolic systems.
I'm sure several people in this newsgroup do. I have a good collection of
his
papers that span early 60s until the early 90s. But even further back was
the
work of Chance (I presume Garfinkel was one of his students) and Hess. From
my archeological expeditions to the library I have concluded that the first
paper
on computer simulation in biochemistry was back in 1943 by Chance where
he used a mechanical differential analyzer to simulate time courses of
peroxidase.
Chance, B. (1943) The kinetics of the enzyme-substrate compound of
peroxidase.
J. Biol. Chem. 151, 553-577.
The interesting thing about this paper is that it predates digital computers
(even
electrical analogs!), simulations of protein structure, and even the
discovery of the
structure of DNA... (and was published during WW II). I am very interested
in
finding an even earlier biochemical simulation paper.
> It failed, more or less, because the *numerical methods* were not mature
> enough then. I wonder what other contributors to this forum think about
> the significance of Garfinkel's work.
I'm not sure it failed only because of the numerical methods. In fact,
Garfinkel's
group helped highlight the problem of stiffness and eventually used stiff
integrators. I think the biggest problem that Garfinkel's work encountered
(and other groups later on) is one that has not yet been solved completely:
they were integrating parameters studied in vitro (and in isolation) in a
system.
It turns out that several of these parameters are not applicable to the
system
because of fundamental differences between cells and test tubes
(concentrations,
organization, etc.). I think that simulations of really large biochemical
networks
will be much more accurate when we do the parameter estimation in the actual
real system.
> My other question, similar in nature, has to do with this book:
>> -----------------
> @book {Haya85,
> author = "K. Hayashi and N. Sakamoto",
> title = "Dynamic Analysis of Enzyme Systems -- An Introduction",
> publisher = "Springer-Verlag", address = "New York", year = "1985"}
> -----------------
>> Is there anybody reading this who was significantly influenced by this
> book?
Yup! I was. Sakamoto is still active (maybe even reading this newsgroup).
He has recently done a sabattical at Marta Cascante's lab in Barcelona.
Oh, and by the way, if you had not yet noticed from the header, I have moved
east and am now a Research Scientist at Virginia Tech.
Pedro Mendes
