From Protein Structure to Function with Bioinformatics.pdf
From Protein Structure to Function with Bioinformatics.pdf
From Protein Structure to Function with Bioinformatics.pdf
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Chapter 10Integrated Servers for <strong>Structure</strong>-Informed<strong>Function</strong> PredictionRoman A. LaskowskiAbstract No single method for predicting a protein’s function from its threedimensionalstructure is perfect; some methods work well in some cases, whereasother methods perform better in others. Consequently, it makes sense <strong>to</strong> applya number of different predictive methods <strong>to</strong> a given protein structure and obtaineither a consensus or the most likely prediction from them all. In this chapter wedescribe two web servers, ProKnow (http://proknow.mbi.ucla.edu) and ProFunc(http://www.ebi.ac.uk/profunc), that use a cocktail of methods for predicting functionfrom 3D structure.10.1 IntroductionPredicting the function of a newly solved protein structure is a bit like trying <strong>to</strong>solve a tantalizing detective mystery. The 3D structure undoubtedly holds the clues<strong>to</strong> what the protein does; but the problem is how <strong>to</strong> identify those clues, how <strong>to</strong>assess their reliability, how <strong>to</strong> spot and discard any red herrings, and how <strong>to</strong> piecethe remaining clues <strong>to</strong>gether <strong>to</strong> arrive at the final solution of the mystery.This problem has really only arisen fairly recently as a direct result of the variousStructural Genomics (SG) initiatives that were started up at the start of thisdecade. Before then, experimentalists would already know much about their proteinbefore embarking on determination of its 3D structure and would have selected itfor its biological interest. Much of the point of solving the structure was <strong>to</strong> gain aninsight in<strong>to</strong> how the protein achieved its biological function at the a<strong>to</strong>mic level. Themotivation of the SG groups, <strong>with</strong> their high-throughput structure determinationmethods, differed markedly. Now a protein would be solved if it belonged <strong>to</strong> a family<strong>with</strong> no structural representatives, or was expected <strong>to</strong> have a novel fold, or was relevant<strong>to</strong> some disease. Knowledge of its function no longer came in<strong>to</strong> it.R.A. LaskowskiEuropean <strong>Bioinformatics</strong> Institute, Wellcome Trust Genome Campus, Hinx<strong>to</strong>n, Cambridge,CB10 1SD, UKe-mail: roman@ebi.ac.ukD.J. Rigden (ed.) <strong>From</strong> <strong>Protein</strong> <strong>Structure</strong> <strong>to</strong> <strong>Function</strong> <strong>with</strong> <strong>Bioinformatics</strong>, 251© Springer Science + Business Media B.V. 2009
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