Multiple weak hits confuse complex systems: a transcriptional regulatory network as an example.
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.
Agoston
Vilmos
V
Szeged Biological Research Center, P.O. Box 521, H-6701 Szeged, Hungary. vilagos@nucleus.szbk.u-szeged.hu
Csermely
Péter
P
Pongor
Sándor
S
D003198:Computer Simulation; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008954:Models, Biological; D015202:Protein Engineering / Q000379:methods; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
D029968:Escherichia coli Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors