Deconvolution of a multi-component interaction network using systems chemistry

Chemical events that transform a complex system from one well defined state into a different well defined state are of critical importance in both biotic and abiotic systems[1-3]. For example, inside the cellular environment, signal transduction proceeds through a sequence of steps that transforms the system from one state to a completely different state. In single cell and multi-cellular organisms these signal transduction pathways are typically guided by various protein-protein interactions that are in turn controlled by genetic regulatory networks. A recent study revealed that the transcription regulatory networks in yeast Saccharomyces cerevisiae involve 4549 physical interactions between 3278 yeast proteins where as genetic regulatory network is formed 1289 directed positive or negative direct transcriptional regulations within a set of 68 proteins[4,5]. Such protein-protein interaction networks define pathways for the propagation of various signals such as phosphorylation and allosteric regulation of proteins. Another study on Escherichia coli was able to identify 1079 regulatory interactions out of which 741 interactions are involved in the network that regulate of amino acid biosynthesis, flagella biosynthesis, osmotic stress response, antibiotic resistance, and iron regulation[6]. The complex network of interactions that characterizes biological systems results in remarkable emergent properties that ultimately give rise to life itself.The success of systems biology[1,7-11] in the reconstruction of complex functional systems based on a fundamental understanding of the behavior of a series of biological components has served as a stimulus for chemists to begin to develop systems chemistry with the goal of creating functional systems by combining the behaviors of well characterized chemical building blocks[12-14]. For example, the Ghadiri group has explored the behavior of complex systems comprising peptides, enzyme, and/or DNA toward the construction of syste