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Integrated Strategy

Integrated Strategy

The Scientific Cores provide essential intellectual, computational, and experimental infrastructure for development of a general sequence/structure based stategy for functional assignment.  While the Scientific Cores are the intellectual and technological center of the EFI, the Bridging Projects serve to test and calibrate the functional predictions from the Scientific Cores. The Bridging Projects evaluate predicted functions using custom, focused libraries of substrates, products, and analogs to screen for in vitro functions.  Such validation is essential to the successful development of a general strategy which will be broadly applicable to proteins from any superfamily thus providing the maximum benefit to the scientific community.  Finally, Data and Dissemination Core ensures the EFI findings, data, and tools are appropriately distributed to the wider community.

The integrated strategy developed by the EFI for functional assignment of unknown enzymes is summarized below:

1) identify functional assignment projects based on sequence, operon, and pathway analyses using sequence similarity networks and bioinformatic data (All EFI Members)

2) select targets to achieve appropriate sampling of enzymes with a putative function (All EFI Members)

3a) experimentally evaluate selected targets by providing samples (Protein Core) for activity measurement (Bridging Projects) and structural characterization (Structure Core)

3b) computationally evaluate selected targets through homology modeling (if needed) and in silico ligand docking to generate rank-ordered lists of predicted substrates (Computation Core)  

4)  analyze results from experimental and computational work to determine function and refine functional assignment strategies  (All EFI Members)

5) when possible, elucidate in vivo function through focused genetics, transcriptomics, and metabolomics or any combination thereof (Microbiology Core)  

6) annotation transfer to receptive public databases and dissemination of new functions and resulting strategies (Data and Dissemination Core)