Evidence map›Paper›PMID 20506260›Full record

ArticleProtein science : a publication of the Protein Society2010

Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation.

A D Wilkins, R Lua, S Erdin, R M Ward, O Lichtarge

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

16 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. The use of evolutionary patterns in protein annotation.Current opinion in structural biology · 2012
    Review
  10. Article
  11. Evolutionary trace for prediction and redesign of protein functional sites.Methods in molecular biology (Clifton, N.J.) · 2012
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Prediction and redesign of protein-protein interactions.Progress in biophysics and molecular biology
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

A D WilkinsDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
R Lua
S Erdin
R M Ward
O Lichtarge

Funding

TRAINING PROGRAM IN COMPUTATIONAL BIOLOGY AND MEDICINET15LM007093 · NLM · RICE UNIVERSITY · PI Lydia E. Kavraki · 1992 to 2026
$20.8M
Functional Determinnats in G Protein-coupled ReceptorsR01GM066099 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI LICHTARGE, OLIVIER · 2003 to 2022
$7.5M
Comparative genomics of protein structure and functionR01GM079656 · NIGMS · BAYLOR COLLEGE OF MEDICINE · PI LICHTARGE, OLIVIER · 2007 to 2019
$4.3M
NIGMS NIH HHS GM066099NIGMS NIH HHS GM079656NLM NIH HHS 5T15LM07093NLM NIH HHS T15 LM007093
6 · The paper itself

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.

Indexed as

AlgorithmsAmino Acid SequenceComputational BiologyModels, MolecularProtein ConformationProteinsProtein Structure, SecondaryProtein Structure, TertiaryProteins

Identifiers

PMID20506260
PMCPMC2974822

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.