Investigators at Burnham Institute for Medical Research (Burnham), University of California, San Diego, The Scripps Research Institute (TSRI), Genomics Institute of the Novartis Research Foundation (GNF) and other institutions have constructed a complete model, including three dimensional protein structures, of the central metabolic network of the bacterium Thermotoga maritima (T. maritima). This is the first time scientists have developed such a comprehensive model of a metabolic network overlaid with an atomic resolution of network proteins. The analysis of the model, among others, highlights the important role of a small number of essential protein shapes, lending new insights into the evolution of protein networks and the functions within these networks. The study was published in the journal Science on September 18.
Combining biochemical studies, structural genomics and computer modeling, the researchers deciphered the shapes, functions and interactions of 478 proteins that make up T. maritima’s central metabolism. The team also found connections between these proteins and 503 unique metabolites in 562 intracellular and 83 extracellular metabolic reactions.
“We have built an actual three dimensional model of every protein in the central metabolic system,” said Adam Godzik, Ph.D., director of Burnham’s Bioinformatics and Systems Biology program. “We got the whole thing. This is analogous to sequencing an entire genome.”
With this data, scientists can simulate metabolism simultaneously on a biochemical and molecular level. This information has the promise to expand computer modeling to allow investigators to simulate the interactions between proteins and various compounds in an entire system. Furthermore, the procedure developed in this study could be applied to study many other organisms, including humans.