Multiple, weak hits confuse complex systems A transcriptional regulatory network as an exam.pdfVIP

/q-bio.MN/0410026 Phys. Rev. E. 71, 051909 (2005) Multiple, weak hits confuse complex systems: A transcriptional regulatory network as an example 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 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. I. INTRODUCTION Due to the general applicability of network models [1-3], network damage has become a widely examined phenomenon in various fields. Scale-free networks have been shown to be relatively insensitive to random damage. However, they are rather vulnerable to attacks targeted to their most-connected elements, called hubs [4]. In several networks cascading failures may occur [5-7] and the effects of network topology [4,7-11] permanent damage [12] on the resistance of networks have been examined. Most of the above studies used a complete elimination of an element from the network to assess network stability. Here we would li