PMID:16089573
| Citation |
Agoston, V, Csermely, P and Pongor, S (2005) Multiple weak hits confuse complex systems: a transcriptional regulatory network as an example. Phys Rev E Stat Nonlin Soft Matter Phys 71:051909 |
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| Abstract |
Robust systems, like the molecular networks of living cells, are often resistant to single hits such as those caused by high-specificity drugs. Here we show that partial weakening of the Escherichia coli and Saccharomyces cerevisiae transcriptional regulatory networks at a small number (3-5) of selected nodes can have a greater impact than the complete elimination of a single selected node. In both cases, the targeted nodes have the greatest possible impact; still, the results suggest that in some cases broader specificity compounds or multitarget drug therapies may be more effective than individual high-affinity, high-specificity ones. Multiple but partial attacks mimic well a number of in vivo scenarios and may be useful in the efficient modification of other complex systems. |
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| Keywords |
Computer Simulation; Escherichia coli Proteins/genetics; Escherichia coli Proteins/metabolism; Gene Expression Regulation/physiology; Models, Biological; Protein Engineering/methods; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Signal Transduction/physiology; Transcription Factors/metabolism; Transcriptional Activation/physiology |
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