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

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.

8 pages, 3 figures, 2 tables

References in corpus (3)

• The efficiency of multi-target drugs: the network approach might help drug design
• Cascade control and defense in complex networks
• Water and molecular chaperones act as weak links of protein folding networks: energy landscape and punctuated equilibrium changes point towards a game theory of proteins

Cited by in corpus (1)

• The efficiency of multi-target drugs: the network approach might help drug design