Predicting the points of interaction of small molecules in the NF-κB pathway

Clusters that contain compounds with a predominant interaction within the pathway were created, which were then used to predict the interaction of compounds not included in the clustering analysis.The technique successfully predicted the points of interactions of compounds that are known to interact with the NF-κB pathway. The method was also shown to be successful when compounds for which the interaction points were unknown were included in the clustering analysis.A major challenge of systems biology is to use computational modelling to predict new targets for chemical intervention. Systems biology involves the quantitative analysis and integration of individual components of a biological system leading to a better understanding of the dynamic and regulatory properties of the system[1-3]. Chemical biology, on the other hand, involves the screening of a set of chemical entities to determine their effects on the function of a system. The combination of these approaches can allow a better understanding of the system network through the identification of new cellular reactions at which new chemical entities perturb the system[4-6]. Figure 1 outlines the methodology involved.One of the most studied cellular signalling systems is the Nuclear Factor κB (NF-κB) network. The NF-κB family of transcription factors controls the transcription of at least 300 genes, but has different transcriptional and cell fate outcomes in different cells and in response to different stimuli. As well as being a critical component of the innate immune response, NF-κB controls cell division and apoptosis in most cell types. While the NF-κB signalling pathway has been studied in many papers (nearly 30,000 are returned by a PubMed search for "Nuclear Factor kappa B"), there is still a great deal about the system which is not understood. Recently, NF-κB proteins have been shown to oscillate between the cytoplasm and nucleus of stimulated cells[7] and the frequency of these oscillations has been sug