Mike Cantor wrote:
> 4. What is really the role of all of the metabolic simulation software
> packages I see out there, such as Gepasi, SCAMP, Mist, DBSolve, Kinsim,
> SCOP, etc. Are these widely used? What factors have led to their adoption?
I am not qualified to address many of the larger issues you are
interested in discussing, but I'd like to say something about the
program KINSIM. KINSIM [Bars8334] is used with the rate of
approximately 30 journal article citations per year. The reason for its
adoption, in my opinion, is tradition and (originally, in the early
1980's) clever publicity by the authors. Apparently, around 1984 Carl
Frieden sent out VAX tapes with the FORTRAN "deck" of the program to a
lot of people. (That was before PCs, if you can imagine that
paleolithic era.)
I looked at KINSIM about six years ago and found that it contains
serious numerical flaws in two areas. The first design flaw has to do
with the computation of multiple simultaneous biochemical equilibria,
using a variation of the Storer and Cornish-Bowden [Stor7601]
fixed-point method. I corresponded with Frieden about this and showed
him where the errors were. I assume that if there is a maintenance
upgrade of the KINSIM code, the problem may have gotten fixed - I don't
know.
The second design problem was in the companion FITSIM [Zimm8981]
module. I found that regression analyses of experimental enzyme kinetic
data were producing completely wrong values of kinetic constants. One
example of such behavior is documented in my own paper describing the
program DYNAFIT [Kuzm9660]. In that paper you will see that the
KINSIM/FITSIM values for the kinetics of HIV-protease inhibition are
wrong by several orders of magnitude.
----
The bottom of my post is this: if you were to include in your literature
review the work done with KINSIM, it might be important to cite (excuse
the shameless plug) my own paper [Kuzm9660] on DYNAFIT showing that
KINSIM can produce wrong answers. This might save some other people
besides me quite a bit of frustration. You may even consider looking at
the use of DYNAFIT in the literature. As far as I know, there might be
between 100 and 200 journal articles that cite the program in the area
of simulation and/or statistical analysis of enzyme kinetic data.
Hope this helps,
- Petr
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
@article {Bars8334,
author = "B. A. Barshop and R. W. Wrenn and C. Frieden",
title = "Analysis of numerical methods for computer simulations
of complex kinetic processes: development of {KINSIM}",
journal = "Anal. Biochem.",
volume = "130",
pages = "134--145",
year = "1983"}
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
@article {Zimm8981,
author = "C. T. Zimmerle and C. Frieden",
title = "Analysis of progress curves by simulations generated by
numerical integration",
journal = "Biochem. J.",
volume = "258",
pages = "381-387",
year = "1989"}
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
@article {Stor7601,
author = "A. C. Storer and A. Cornish-Bowden",
title = "Concentration of $ {\rm MgATP}^ {2-}$ and other ions
insolution. {C}alculation of the true concentrations of species present
in mixtures of associating ions",
journal = "Biochem. J.",
volume = 159,
pages = "1--5",
year = 1976}
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
@article {Kuzm9660,
author = "P. Kuzmi\v{c}",
title = "Program {DYNAFIT} for the analysis of enzyme kinetic data:
{A}pplication to {HIV} proteinase",
journal = "Anal. Biochem.",
volume = "237",
pages = "260--273",
year = "1996" }
_____________________________________________________________________
P e t r K u z m i c, Ph.D. mailto:pkuzmic at biokin.com
BioKin Ltd. * Software and Consulting http://www.biokin.com
