ArticleProtein science : a publication of the Protein Society2010
Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation.
Article in Protein science : a publication of the Protein Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Integrative exome sequencing and machine learning identify MICB and interferon pathway genes as contributors to SSc risk.Annals of the rheumatic diseases · 2025Article
- A general calculus of fitness landscapes finds genes under selection in cancers.Genome research · 2022Article
- Identification of evolutionarily stable functional and immunogenic sites across the SARS-CoV-2 proteome and greater coronavirus family.Bioinformatics (Oxford, England) · 2021Article
- Identification of evolutionarily stable functional and immunogenic sites across the SARS-CoV-2 proteome and the greater coronavirus family.Research square · 2021Article
- Sequence-structure-function relationships in class I MHC: A local frustration perspective.PloS one · 2020Article
- UET: a database of evolutionarily-predicted functional determinants of protein sequences that cluster as functional sites in protein structures.Nucleic acids research · 2016Article
- 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
- The use of evolutionary patterns in protein annotation.Current opinion in structural biology · 2012Review
- Article
- Evolutionary trace for prediction and redesign of protein functional sites.Methods in molecular biology (Clifton, N.J.) · 2012Article
- Separation of recombination and SOS response in Escherichia coli RecA suggests LexA interaction sites.PLoS genetics · 2011Article
- Protein function prediction: towards integration of similarity metrics.Current opinion in structural biology · 2011Review
- Article
- PyETV: a PyMOL evolutionary trace viewer to analyze functional site predictions in protein complexes.Bioinformatics (Oxford, England) · 2010Article
- Prediction and redesign of protein-protein interactions.Progress in biophysics and molecular biologyReview
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5 authors.
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Abstract
Protein functional sites control most biological processes and are important targets for drug design and protein engineering. To characterize them, the evolutionary trace (ET) ranks the relative importance of residues according to their evolutionary variations. Generally, top-ranked residues cluster spatially to define evolutionary hotspots that predict functional sites in structures. Here, various functions that measure the physical continuity of ET ranks among neighboring residues in the structure, or in the sequence, are shown to inform sequence selection and to improve functional site resolution. This is shown first, in 110 proteins, for which the overlap between top-ranked residues and actual functional sites rose by 8% in significance. Then, on a structural proteomic scale, optimized ET led to better 3D structure-function motifs (3D templates) and, in turn, to enzyme function prediction by the Evolutionary Trace Annotation (ETA) method with better sensitivity of (40% to 53%) and positive predictive value (93% to 94%). This suggests that the similarity of evolutionary importance among neighboring residues in the sequence and in the structure is a universal feature of protein evolution. In practice, this yields a tool for optimizing sequence selections for comparative analysis and, via ET, for better predictions of functional site and function. This should prove useful for the efficient mutational redesign of protein function and for pharmaceutical targeting.
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