Evidence map›Paper›PMID 25115701›Full record

ArticleAngewandte Chemie (International ed. in English)2014

A designed conformational shift to control protein binding specificity.

Servaas Michielssens, Jan Henning Peters, David Ban, Supriya Pratihar, Daniel Seeliger, Monika Sharma, Karin Giller, Thomas Michael Sabo, Stefan Becker, Donghan Lee and 2 more

Abstract read
In one paragraph

Article in Angewandte Chemie (International ed. in English), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed.

  1. Article
  2. Improving Conformational Ensembles of Folded Proteins in Go̅Martini.Journal of chemical theory and computation · 2026
    Article
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  13. Harnessing Conformational Plasticity to Generate Designer Enzymes.Journal of the American Chemical Society · 2020
    Review
  14. Article
  15. Membranes as the third genetic code.Molecular biology reports · 2020
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

12 authors.

Servaas MichielssensComputational Biomolecular Dynamics Group, Max Planck Institute for Biophysical Chemistry, Am Faßberg 11, 37077 Göttingen (Germany) http://www.mpibpc.mpg.de/groups/de_groot/
Jan Henning Peters
David Ban
Supriya Pratihar
Daniel Seeliger
Monika Sharma
Karin Giller
Thomas Michael Sabo
Stefan Becker
Donghan Lee
Christian Griesinger
Bert L de Groot

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In a conformational selection scenario, manipulating the populations of binding-competent states should be expected to affect protein binding. We demonstrate how in silico designed point mutations within the core of ubiquitin, remote from the binding interface, change the binding specificity by shifting the conformational equilibrium of the ground-state ensemble between open and closed substates that have a similar population in the wild-type protein. Binding affinities determined by NMR titration experiments agree with the predictions, thereby showing that, indeed, a shift in the conformational equilibrium enables us to alter ubiquitin's binding specificity and hence its function. Thus, we present a novel route towards designing specific binding by a conformational shift through exploiting the fact that conformational selection depends on the concentration of binding-competent substates.

Indexed as

Molecular Dynamics SimulationNuclear Magnetic Resonance, BiomolecularPoint MutationProtein BindingThermodynamicsUbiquitinUbiquitinmolecular dynamicsprotein designprotein-protein interactionsubiquitin

Identifiers

PMID25115701
PMCPMC4497613

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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.