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Hiro,

First, promoter example is a bit dangerous one, as it makes heavy use of
biological abstractions. It is obviously one of the many points where
cannonical biochemical paradigm fails ( at least feasibly) to model
biological systems. Having said that, I think it is much better to model
promoter binding as DNA-protein complexes. Something very similar to
Jeremy's dimer example. My arguments for this is as follows:
There are in fact four different possible reactions satisfying your
example : no A bound ( it just floated around), A bound to promoter site
1, A bound to promoter site 2, A bound to both. One may wish to strech
biochemical paradigm and say that this representation only denotes the
last one. But what if there were not two but three promoter sites? The
beauty with real stochiometry constants is that reaction either occurs
in this ratio, or does not occur at all. This simply does not hold for
modifiers; even when there are no modifiers, the reaction still occurs (
at least "so called" reversible ones).

Please do not get me wrong, I am not saying that we should not capture
qualitative mechanisms. On the contrary, I am actually working on
qualitative models. What I am saying that we should have a better system
to capture such information, and as Jeremy also pointed out, modeling
intermediary complexes looks like the most natural one.

Best,
Emek

Hiroyuki Kuwahara wrote:

>Suppose there is a promoter which has 2 operators. And suppose species A
>binding to operator 1 and another A binding to operator 2 helps RNAP bind and begin
>transcription of some gene. If this is specified by Shea/Ackers model,
>then shouldn't A be a modifier and the stoichiometry be 2?
>
>Will this be awkward to biologist?
>
>Thanks,
>
>Hiro
>
>
>
>> a) Modifier stochiometry does not exist in cannonical biochemical
>>paradigm, so will be awkward to any biologist.
>> b) If say two co-factors is needed to bind to a certain compound,
>>then one can always model them as complex formations. If the knowledge
>>is qualitative, then you do not need to worry about constants of
>>complex formation reaction. Although currently SBML have some
>>limitations for complex formations, it looks like it will get much
>>better in this aspect at level 3.
>> c) If you have quantitative knowledge, then as the original post
>>mentions, we do not need modifiers.
>>
>>Just my two cents,
>>
>>Emek
>>
>>Pedro Mendes wrote:
>>
>>
>>
>>>I'm rather intrigued by this "modifier stoichiometry". Modifiers do not even
>>>have to bind anything, so I don't think the concept of stoichiometry
>>>applies here. The way in which a modifier modifies the rate of reaction is
>>>explicit on the rate law.
>>>
>>>Pedro
>>>
>>>On Monday 25 April 2005 12:56 pm, Hiroyuki Kuwahara wrote:
>>>
>>>
>>>
>>>
>>>>Hi,
>>>>
>>>>I'd just like to know why SBML does not support stoichiometries of
>>>>modifiers. This is fine for ODE simulation, but not for discrete
>>>>stochastic simulation. The workaround, of course, is to express a
>>>>modifier as both a reactant and a product with an appropriate
>>>>stoichiometry. But if this is how it's supposed to be,
>>>>then we don't even need a modifier field.
>>>>
>>>>Thanks,
>>>>
>>>>Hiro
>>>>
>>>>
>>>>
>>>>
>>>
>>>
>>>
>>>
>>
>>
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