ArticlePloS one2008
De-orphaning the structural proteome through reciprocal comparison of evolutionarily important structural features.
Article in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Prediction and experimental validation of enzyme substrate specificity in protein structures.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Accounting for epistatic interactions improves the functional analysis of protein structures.Bioinformatics (Oxford, England) · 2013Article
- Function prediction from networks of local evolutionary similarity in protein structure.BMC bioinformatics · 2013Article
- ETAscape: analyzing protein networks to predict enzymatic function and substrates in Cytoscape.Bioinformatics (Oxford, England) · 2012Article
- The use of evolutionary patterns in protein annotation.Current opinion in structural biology · 2012Review
- Evolutionary trace for prediction and redesign of protein functional sites.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Desmosterolosis-phenotypic and molecular characterization of a third case and review of the literature.American journal of medical genetics. Part A · 2011Review
- Protein function prediction: towards integration of similarity metrics.Current opinion in structural biology · 2011Review
- Article
- Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation.Protein science : a publication of the Protein Society · 2010Article
- Evolution: a guide to perturb protein function and networks.Current opinion in structural biology · 2010Review
- Evolution-guided discovery and recoding of allosteric pathway specificity determinants in psychoactive bioamine receptors.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Evolutionary trace annotation of protein function in the structural proteome.Journal of molecular biology · 2010Article
- Comparison of structure-based and threading-based approaches to protein functional annotation.Proteins · 2010Article
- Identification of family-specific residue packing motifs and their use for structure-based protein function prediction: I. Method development.Journal of computer-aided molecular design · 2009Article
- Mitochondrial neurogastrointestinal encephalopathy due to mutations in RRM2B.Archives of neurology · 2009Article
- FINDSITE: a combined evolution/structure-based approach to protein function prediction.Briefings in bioinformatics · 2009Review
- Evolutionary Trace Annotation Server: automated enzyme function prediction in protein structures using 3D templates.Bioinformatics (Oxford, England) · 2009Article
- Protein function annotation by homology-based inference.Genome biology · 2009Review
- Protein meta-functional signatures from combining sequence, structure, evolution, and amino acid property information.PLoS computational biology · 2008Article
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Authors and funding
6 authors.
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Abstract
Function prediction frequently relies on comparing genes or gene products to search for relevant similarities. Because the number of protein structures with unknown function is mushrooming, however, we asked here whether such comparisons could be improved by focusing narrowly on the key functional features of protein structures, as defined by the Evolutionary Trace (ET). Therefore a series of algorithms was built to (a) extract local motifs (3D templates) from protein structures based on ET ranking of residue importance; (b) to assess their geometric and evolutionary similarity to other structures; and (c) to transfer enzyme annotation whenever a plurality was reached across matches. Whereas a prototype had only been 80% accurate and was not scalable, here a speedy new matching algorithm enabled large-scale searches for reciprocal matches and thus raised annotation specificity to 100% in both positive and negative controls of 49 enzymes and 50 non-enzymes, respectively-in one case even identifying an annotation error-while maintaining sensitivity ( approximately 60%). Critically, this Evolutionary Trace Annotation (ETA) pipeline requires no prior knowledge of functional mechanisms. It could thus be applied in a large-scale retrospective study of 1218 structural genomics enzymes and reached 92% accuracy. Likewise, it was applied to all 2935 unannotated structural genomics proteins and predicted enzymatic functions in 320 cases: 258 on first pass and 62 more on second pass. Controls and initial analyses suggest that these predictions are reliable. Thus the large-scale evolutionary integration of sequence-structure-function data, here through reciprocal identification of local, functionally important structural features, may contribute significantly to de-orphaning the structural proteome.
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