The Enzyme Function Initiative (EFI) is developing a robust sequence/structure‑based strategy for facilitating discovery of in vitro enzymatic and in vivo metabolic/physiological functions of unknown enzymes discovered in genome projects, a crucial limitation in genomic biology. This goal will be accomplished by integrating bioinformatics, structural biology, and computation with enzymology, genetics, and metabolomics.
The EFI has established five Scientific Cores for: 1) directing target selection as well as devising strategies for functional assignment based on sequence relationships and genome context; 2) cloning, expression, and purification of targets; 3) experimental determination of structures of targets; 4) homology modeling and in silico docking of ligand libraries for targets; and 5) microbiological and metabolomic characterization of the in vivo roles of targets.
The functional predictions are tested by five Bridging Projects that focus on functionally diverse superfamilies. While each of these superfamilies share conserved partial reactions, the identities of the substrates/products are not conserved and functional assignment cannot be accomplished by transfer of prior annotations based only on sequence or structural similarity.
The EFI is funded by a Large-Scale Collaborative Project (Glue Grant) from the National Institute of General Medical Sciences (U54 GM093342). The EFI is formed from 14 researchers from 9 academic institutions in the US.