Ramakrishnan, Naren ; Bhalla, Upinder S. (2008) Memory switches in chemical reaction space PLoS Computational Biology, 4 (7). pp. 1-9. ISSN 1553-734X
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Official URL: http://www.ploscompbiol.org/article/info%3Adoi%2F1...
Related URL: http://dx.doi.org/10.1371/journal.pcbi.1000122
Just as complex electronic circuits are built from simple Boolean gates, diverse biological functions, including signal transduction, differentiation, and stress response, frequently use biochemical switches as a functional module. A relatively small number of such switches have been described in the literature, and these exhibit considerable diversity in chemical topology. We asked if biochemical switches are indeed rare and if there are common chemical motifs and family relationships among such switches. We performed a systematic exploration of chemical reaction space by generating all possible stoichiometrically valid chemical configurations up to 3 molecules and 6 reactions and up to 4 molecules and 3 reactions. We used Monte Carlo sampling of parameter space for each such configuration to generate specific models and checked each model for switching properties. We found nearly 4,500 reaction topologies, or about 10% of our tested configurations, that demonstrate switching behavior. Commonly accepted topological features such as feedback were poor predictors of bistability, and we identified new reaction motifs that were likely to be found in switches. Furthermore, the discovered switches were related in that most of the larger configurations were derived from smaller ones by addition of one or more reactions. To explore even larger configurations, we developed two tools: the bistabilizer, which converts almost-bistable systems into bistable ones, and frequent motif mining, which helps rank untested configurations. Both of these tools increased the coverage of our library of bistable systems. Thus, our systematic exploration of chemical reaction space has produced a valuable resource for investigating the key signaling motif of bistability.
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|Deposited On:||13 Oct 2010 17:08|
|Last Modified:||16 May 2011 15:17|
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