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

Vilmos Ágoston, Péter Csermely, and Sándor Pongor
Phys. Rev. E 71, 051909 – Published 26 May 2005

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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  • Received 22 October 2004

DOI:https://doi.org/10.1103/PhysRevE.71.051909

©2005 American Physical Society

Authors & Affiliations

Vilmos Ágoston1,*, Péter Csermely2,†, and Sándor Pongor1,3,‡

  • 1Szeged Biological Research Center, P.O. Box 521., H-6701 Szeged, Hungary
  • 2Department of Medical Chemistry, Semmelweis University, P.O. Box 260., H-1444 Budapest 8, Hungary
  • 3International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy

  • *Electronic address: vilagos@nucleus.szbk.u-szeged.hu
  • Electronic address: csermely@puskin.sote.hu
  • Electronic address: pongor@icgeb.org

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Issue

Vol. 71, Iss. 5 — May 2005

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