From Protein Structure to Function with Bioinformatics.pdf

11 Function Predictions of Structural Genomics Results 28711.4 Community AnnotationThe large numbers of protein structures produced by structural genomics haveunfortunately not been associated with equally large numbers of related publications.In fact, the publication of structures is now seen as one of the key bottlenecksin the high-throughput structure determination pipelines (Rigden 2006). This doesnot reflect a lack of interest in publication, poor target selection or a lack of interestingstructures. Rather, it reflects the fact that many of the structural genomics initiativesare required as part of their funding to rapidly deposit and release their data tothe public. This means that the often time consuming prediction or experimentaldetermination of function is performed after release of the structure, often in collaborationwith other laboratories which specialise in the particular protein beingstudied. One way to deal with this bottleneck has been to reduce the time taken toperform the experiments by developing high-throughput experimental screens forenzymatic activities (Kuznetsova et al. 2005). This has shown some success(Proudfoot et al. 2004) but its limitations to assaying a number of key enzyme reactionsmean it cannot yet be applied to more generic function determination. A newapproach to improve the annotation of proteins solved by structural genomics hasbeen to explore the possibility of community-wide annotation of these proteinsusing wikis (Giles 2007; Mons et al. 2008).One of the first such attempts has been the TOPSAN (The Open ProteinStructure Annotation Network) project initiated by the Joint Centre for StructuralGenomics (JCSG), which now includes entries for structures solved by the MidwestCentre for Structural Genomics (MCSG) and the New York SGX Research Centerfor Structural Genomics (NYSGXRC). The project takes the form of a wiki (foundat http://www.topsan.org/) that is viewable by anyone, although only registeredusers can annotate the pages. The idea behind TOPSAN is that collective annotationby a global community of experts, each specialising in their particular areas,can provide much more comprehensive knowledge about all the available proteinssolved than any one individual or small group ever could. The annotation pageswould therefore offer the wider community a combination of automatically generatedand expert-curated annotations of protein structures. The initial prototype versionis now being scaled up to include all structural genomics targets from theProtein Structure Initiative (PSI).A more large scale effort is that of the PDBWiki (http://pdbwiki.org/), whichwas created in August 2007 by the Structural Proteomics Group at the Max-Planck-Institute for Molecular Genetics. This time the focus of the project was every structuredeposited in the PDB, each page providing basic information on the protein alongwith a number of links to other databases and a variety of sequence and structureanalysis tools.This has been taken a step further with a new PDB-based wiki calledProteopedia (http://www.proteopedia.org/). The primary aim of this service is topresent structural and functional knowledge about macromolecules, in a mannerthat is readily accessible to students, scientists and the public. Every entry in the