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Multiple, weak hits confuse complex systems: A transcriptional regulatory network as an example

Vilmos Agoston·Peter Csermely·Sandor Pongor
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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) 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 broad 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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Vilmos Agoston, Peter Csermely, Sandor Pongor. 2005-06-11. Multiple, weak hits confuse complex systems: A transcriptional regulatory network as an example. https://doi.org/10.1103/physreve.71.051909

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