Functional differentiation of proteins: implications for structural genomics.
Structural genomics is a broad initiative of various centers aiming to provide complete coverage of protein structure space. Because it is not feasible to experimentally determine the structures of all proteins, it is generally agreed that the only viable strategy to achieve such coverage is to carefully select specific proteins (targets), determine their structure experimentally, and then use comparative modeling techniques to model the rest. Here we suggest that structural genomics centers refine the structure-driven approach in target selection by adopting function-based criteria. We suggest targeting functionally divergent superfamilies within a given structural fold so that each function receives a structural characterization. We have developed a method to do so, and an itemized survey of several functionally rich folds shows that they are only partially functionally characterized. We call upon structural genomics centers to consider this approach and upon computational biologists to further develop function-based targeting methods.
Friedberg
Iddo
I
Program in Bioinformatics and Systems Biology, Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA. idoerg@burnham.org <idoerg@burnham.org>
Godzik
Adam
A
D023281:Genomics; D006801:Humans; D005810:Multigene Family; D009687:Nuclear Proteins / Q000737:chemistry / Q000145:classification* / Q000502:physiology*; D010749:Phosphoprotein Phosphatases
D009687:Nuclear Proteins; C400601:PHLPP1 protein, human; D010749:Phosphoprotein Phosphatases