From Protein Structure to Function with Bioinformatics.pdf

Chapter 11Case Studies: Function Predictionsof Structural Genomics ResultsJames D. Watson and Janet M. ThorntonAbstract The development of high-throughput protein structure determinationpipelines by the various Structural Genomics initiatives around the globe hasresulted in the deposition of several thousand protein structures in the Protein DataBank. However, due to the nature of the target selection process and the requirementfor rapid data release, a significant proportion of these structures have little orno functional information. In order to address this problem a vast array of computationalmethods have been developed to predict a protein’s function from its threedimensional structure. The approaches range from large scale fold comparison tohighly specific residue templates, each with its own advantages and disadvantages.Here we look at the application of these methods in Structural Genomics andreview attempts to determine how successful function prediction from structure hasbeen, with specific examples illustrating some of the success stories.11.1 IntroductionGenome sequencing projects around the globe have already provided enormousamounts of data on the genes that are essential to a number of organisms, and thisinformation is expanding rapidly with the large-scale metagenomics projects currentlyunder way (Yooseph et al. 2007). By comparison, the amount of proteinstructure data available lags far behind. Structural genomics aims to bridge thisgap by solving, in a high-throughput manner, a large number of novel structuresthat can be used to model a larger number of sequences (Fox et al. 2008; Service2005). A consequence of this approach has been the deposition of large numbersof structures with little or no functional annotation. This is in direct contrast totraditional structural biology where the function of a protein is often known inadvance and the structure is often solved to identify the biochemical mechanismsand unique subtleties of its action.J.D. Watson and J.M. Thornton*European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton,Cambridgeshire, CB10 1SD, UK*Corresponding author: e-mail: thornton@ebi.ac.ukD.J. Rigden (ed.) From Protein Structure to Function with Bioinformatics, 273© Springer Science + Business Media B.V. 2009