Multiple weak hits confuse complex systems: a transcriptional regulatory network as an example.

Vilmos Agoston; Péter Csermely; Sándor Pongor

doi:10.1103/physreve.71.051909

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Multiple weak hits confuse complex systems: a transcriptional regulatory network as an example.

Vilmos Agoston·Péter Csermely·Sándor 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) 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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Computer Simulation Escherichia coli Proteins Gene Expression Regulation Models, Biological Protein Engineering Saccharomyces cerevisiae Proteins Signal Transduction Transcription Factors Transcriptional Activation Evaluation Study Journal Article Research Support, Non-U.S. Gov't

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Vilmos Agoston, Péter Csermely, Sándor Pongor. 2005-05-26. 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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