From Protein Structure to Function with Bioinformatics.pdf

298 I.A. Cymerman et al.The collections of models in MODBASE and the SWISS-MODEL Repository,together with model resources generated by PSI centres, are accessible via a singleinterface provided by the Protein Model Portal. The Portal is designed to simultaneouslyquery all integrated databases in the search of pre-computed models of thegiven amino acid sequence. The result page presents the list of models deposited inparticular databases and provides access to them.Models generated by human experts (usually difficult cases that require sophisticatedtechniques for model building and identification of the most reliable structureamong alternatives) are deposited within the PMDB database. PMDB isdesigned to provide access to models published in the scientific literature, togetherwith validating experimental data, but the majority of currently released models arepredictions submitted to the CASP experiment. PMDB allows individual predictorsto submit their models along with related supporting evidence. Users can freelyretrieve models referring to the same target protein or to different regions of thesame protein. Available information for each target includes the protein name,sequence and length, organism and, whenever applicable, links to the SwissProtsequence database (http://www.ebi.ac.uk/swissprot/). After the structure of a targetis solved, the database entry is also linked to the experimental structure in the PDB(http://www.rcsb.org/pdb/home/home.do).As well as large-scale general repositories there are also databases dedicated toparticular organisms. One example is DBMODELING (Silveira et al. 2005) – adatabase aimed to serve as platform for drug design against infectious agents. Todate it contains comparative models of proteins encoded in genomes of only twopathogenic organisms, Mycobacterium tuberculosis and Xylella fastidiosa, thecausative agent of citrus variegated chlorosis.12.3 Accuracy and Added Value of Model-Derived PropertiesAlthough a perfect predictor of overall model accuracy has yet to be developed, itis already possible to determine the average accuracy of particular structural modelderivedproperties (SDP). Most proteins rely on intermolecular recognition in orderto perform their tasks, with ligands ranging from small molecules to multi-proteincomplexes. Therefore, surface properties in particular (see Chapters 7 and 8) suchas residue exposure state, accessible surface area, pockets and electrostatic potentialare directly related to the function.The accuracy of prediction of those model-derived properties was addressed inthe large-scale analyses of simple comparative models performed by Chakravartyand Sanchez (Chakravarty et al. 2005). It was shown that the overall accuracy of allanalyzed structural properties drops as a function of template-to-target sequencesimilarity, but that this decrease has different degrees of impact on the accuracy ofdifferent structural features (Table 12.2). For example, alignment errors show negligibleeffect on the correctness of the prediction of accessible surface area (ASA)while the correctness of the electrostatic potential prediction is already affected