From Protein Structure to Function with Bioinformatics.pdf

10 Integrated Servers for Structure-Informed Function Prediction 259In general, ProKnow performs quite well. Its authors tested it on a nonredundantdata set of proteins of known function and found that around 70% of thefunctional annotations were correct (Pal and Eisenberg 2005). Less specific predictions(e.g. hydrolase) tended to be more accurate than more specific ones (e.g. leucylaminopeptidase). The prediction accuracy has been increased slightly by the recentinclusion of Prolinks, not present in the original version, and should improve moreas the coverage of Prolinks increases.10.3 ProFuncThe second integrated server described here is ProFunc (Laskowski et al. 2005b) at theEuropean Bioinformatics Institute (EBI), http://www.ebi.ac.uk/profunc, developed aspart of a collaboration with the Midwest Center for Structural Genomics (MCSG).ProFunc allows the user to either upload a protein structural model or to enter the PDBcode of a structure already in the Protein Data Bank. In the latter case, if ProFunc hasalready been run on that PDB entry, the results will be displayed immediately.When ProFunc runs it applies a number of sequence- and structure-based methodsto the structure, as shown in Fig. 10.4. A processor farm is used, with differentmethods sent to different processors. Several of the compute intensive method arethemselves subdivided to run in parallel on multiple processors. Processing is usuallycomplete within about an hour.The results of each method are then summarized, with further details availablefor each method. However, the results are not combined in any sophisticated way,as is done in ProKnow. Rather, there is a summary at the top of the results pageshowing the most commonly occurring GO terms and protein names, but this ismeant only as a quick guide. The primary aim of the server is to present the resultsin an easily accessible format to enable researchers to interpret them, using theirown expertise and knowledge of the protein in question.Now, although ProFunc does apply a number of sequence-based methods, usingseveral well-known search techniques such as FASTA and InterProScan (Quevillonet al. 2005), we will only describe the structure-based methods here as most of themare unique to this server.10.3.1 ProFunc’s Structure-Based Methods10.3.1.1 Fold-MatchingThe first of the structure-based methods is a search against a representative subsetof the PDB for structures with the same, or similar, overall fold as the target. TheSSM (Secondary Structure Matching) program is used (Krissinel and Henrick2004). It performs a fast graph-matching procedure to compare the secondary struc-