""Michael C. Kohn"" <kohn at valiant.niehs.nih.gov> wrote in message
news:v04210101b68365da4120@[157.98.7.180]...
>> The BIOSSIM package developed by the Garfinkel group in the 1970s
> included a matrix method for computing corrections to the time
> derivatives of the state variables when the corresponding chemicals
> participated in rapid equilibria. These reactions were flagged as
> fast reactions which were assumed to equilibrate on the time scale of
> a single integration step. We used this feature for such processes as
> chelation equilibria and other non-enzymatic reactions. This approach
> minimized the stiffness of the integration and greatly reduced the
> computation time. Also, we assumed that the ligand binding was in a
> quasi-steady state, separated out the ligand binding equations for
> enzymes, and distributed the enzyme forms algebraically. The
> enzymatic rate was then calculated from the instantaneous enzyme
> distribution. This too improved stiffness and sped the computation.
> As far as I know, no one has implemented Park's idea of dynamically
> determining if a reaction is sufficiently fast.
>> Michael C. Kohn
>
I didn't know that about BIOSSIM, I knew it modeled enzymes in mechanistic
detail and then the enzyme rate was calculated from the enzyme species
distribution. I had the opportunity when I did my PhD to look at the BIOSSIM
source which is where I spotted that technique. The new guys on the block
(the 'alternative community' as I call them) have no idea about this stuff,
for what ever reason they don't read about any work that was done before
sequencing took over.
By the way Michael, do you know what ever happened to David Park?
If I had some time I'd have a go an implement David's algorithm. We've got a
model at the moment which is full of equilibrium reactions. I'm not sure how
one should go about this sort of modeling in an automatic way because such
systems admit two moiety groups, one group which comes from the slow
reactions and the other from the quasi-steady-state group, other than David
Park's paper I don't know if anyone has written anything on it. If anyone
knows of any work in this area I'd like to know.
Herbert Sauro
Caltech
