Wolfram
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Molecular interactions in a macrophage
If you would like to know why computers could be needed in lifescience in the future here is a map of molecular interactions in a macrophage:
http://www.signaling-gateway.org/reports/v2/DA0014/ResultsA....
[Edited on 11-11-2004 by chemoleo]
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chemoleo
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Oh, although such maps look really neat and complex, I'd guarantee you that at least a third of these interactions is incorrect (they use such
things as yeast-two hybrid system to determine interactions, which has a high false positive rate), and that at least another of 50% of the
interactions remain yet to be found.
Now, with such an incomplete system of a cell, particularly one that is this complex (involved in the mammalian immune response) do you honestly think
a computer model can, at this point, make any interactions whatsoever?
As far as I know, some pathways (note, not whole cells) have been modelled in bacteria, which are much LESS complex. This has been done with some
success, I am aware of one group in Oxford.
But for mammalian cells - there is a lot that we don't know (yet), and computer models at the most can adapt to existing pathways, but NOT be
able to predict the necessity of this or that protein interaction (unlike, say, calculations that predicted (some time back) that there would be the
need for yet another planet, i.e. Pluto).
Never Stop to Begin, and Never Begin to Stop...
Tolerance is good. But not with the intolerant! (Wilhelm Busch)
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Wolfram
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I think this kind of modeling is really fascinating. I guess thar in reality there would be at least 10x as many interactions in a macrophage.
There are some really nice programs to model interactions many are based on SMBL. Celldesigner is one:
http://www.systems-biology.org/002/
SMBL:
http://www.sbw-sbml.org/index.html
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chemoleo
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I should also say, almost nothing is known about the quantitative strength of the interactions.
INteractions are determined by a variety of assays, some only fish out tight binders, others tight and weak binders, with no ability to discern
between the two.
Therefore, how much of a role do the weak binders really play compared to the tight binders? Have some interactions been discovered simply because
people were looking for them, and finding weak binders with the most sensitive assays? Are these interactions therefore biologically meaningful or
relevant?
Interestingly, my own work currently deals with precisely this question. I wonder at what strength interactions start to become relevant. I suspect
this differs from one biological system to the next. How are we ever going to understand the workings of cells therefore?
Correlating affinity versus functionality is one of the ways to find out. And even that is ridden with artefacts and problems 
[Edited on 25-1-2007 by chemoleo]
Never Stop to Begin, and Never Begin to Stop...
Tolerance is good. But not with the intolerant! (Wilhelm Busch)
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