From Protein Structure to Function with Bioinformatics.pdf

12 Prediction of Protein Function from Theoretical Models 29712.2.2 Databases of ModelsThe efficient exploitation of structural protein models requires their presentation to thescientific community in such a way that they can be used by individual researchers.The establishment of public repositories should encourage the use of protein structuralmodels for guiding bench experiments.Nowadays two kinds of 3D protein structure model databases are widely accessible.Databases such as MODBASE (Pieper et al. 2006) and the SWISS-MODELRepository (Kopp and Schwede 2004) (see Table 12.1) contain models generatedby fully automated procedures. Other databases as PMDB (Protein Model Database)(Castrignano et al. 2006) are designed to provide access to manually built models.Independent of how they were constructed, all databases allow for the web-interfacedretrieval of the model of interest as well as providing supporting informationincluding model reliability assessment and function annotation.To provide accurate models suitable for experimental applications the methodsimplemented by the SWISS-MODEL Repository and MODBASE are based on thecomparative modelling, which is currently the most reliable modelling technique forlarge-scale initiatives. Both databases indicate the level of target-to-templatesequence identity and the SWISS-MODEL Repository has the additional restrictionof including only models with a target-to-template sequence identity higher than40%. The target sequences are selected from the UniProt database (http://www.expasy.uniprot.org/) and both model repositories are regularly updated to ensure thattheir content reflects the current state of sequence and structure databases, integratingnew or modified target sequences, and making use of new template structures. Bothmodel databases provide also the alignments on which the models were based, butthey exploit different methods to evaluate model quality. Models deposited in theSWISS-MODEL Repository are assessed by packing quality of the models by ANOLEA(Melo and Feytmans 1998) and calculation of force field energies by GROMOS96(van Gunsteren 1996) while MODBASE assign the models reliability scores derivedfrom statistical potentials (Melo et al. 2002). The model view mode implemented inthe SWISS-MODEL Repository provides a graphical representation of the InterProfunctional and domain level annotations in the target sequence. MODBASE on theother hand allows for the 3D visualization of putative ligand binding and SNPannotation sites.Table 12.1 Web-accessible databases of pre-computed modelsDatabaseURL http://SWISS-MODEL Repository (Kopp and swissmodel.expasy.org/repository/Schwede 2004)MODBASE (Pieper et al. 2006)salilab.org/modbasePMDB Protein Model Database (Castrignano www.caspur.it/PMDBet al. 2006)Protein Model Portalwww.proteinmodelportal.org/DBMODELING (Silveira et al. 2005)laboheme.df.ibilce.unesp.br/db_modeling/