Evidence map›Paper›PMID 37119820›Full record

ArticleStructure (London, England : 1993)2023

Computational modeling and prediction of deletion mutants.

Hope Woods, Dominic L Schiano, Jonathan I Aguirre, Kaitlyn V Ledwitch, Eli F McDonald, Markus Voehler, Jens Meiler, Clara T Schoeder

Abstract read
In one paragraph

Article in Structure (London, England : 1993), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing 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

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Energetic and structural control of polyspecificity in a multidrug transporter.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Hope WoodsCenter of Structural Biology, Vanderbilt University, Nashville, TN 37235, USA; Chemical and Physical Biology Program, Vanderbilt University, Nashville, TN 37235, USA.
Dominic L SchianoCenter of Structural Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Jonathan I AguirreDepartment of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Kaitlyn V LedwitchCenter of Structural Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Eli F McDonaldCenter of Structural Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Markus VoehlerCenter of Structural Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA.
Jens MeilerCenter of Structural Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA; Institute for Drug Discovery, Leipzig University Medical School, 04103 Leipzig, Germany. Electronic address: jens.meiler@vanderbilt.edu.
Clara T SchoederCenter of Structural Biology, Vanderbilt University, Nashville, TN 37235, USA; Department of Chemistry, Vanderbilt University, Nashville, TN 37235, USA; Institute for Drug Discovery, Leipzig University Medical School, 04103 Leipzig, Germany. Electronic address: clara.schoeder@medizin.uni-leipzig.de.

Funding

Membrane Protein Structure Elucidation from sparse NMR data (KAMP)R01GM080403 · NIGMS · VANDERBILT UNIVERSITY · PI MEILER, JENS · 2007 to 2019
$3.0M
Topological Energetics and the Cellular Quality Control of Integral Membrane ProteinsR01GM129261 · NIGMS · TRUSTEES OF INDIANA UNIVERSITY · PI SCHLEBACH, JONATHAN PATRICK · 2018 to 2022
$1.5M
Console upgrades for biological NMR spectrometersS10RR025677 · NCRR · VANDERBILT UNIVERSITY · PI SANDERS, CHARLES R · 2009 to 2009
$460k
Molecular Chaperone Recognition of CFTR StabilityF31HL162483 · NHLBI · VANDERBILT UNIVERSITY · PI MCDONALD, ELI FRITZ · 2022 to 2023
$58k
NCRR NIH HHS S10 RR025677NHLBI NIH HHS F31 HL162483NIGMS NIH HHS R01 GM080403NIGMS NIH HHS R01 GM129261
6 · The paper itself

Abstract

In-frame deletion mutations can result in disease. The impact of these mutations on protein structure and subsequent functional changes remain understudied, partially due to the lack of comprehensive datasets including a structural readout. In addition, the recent breakthrough in structure prediction through deep learning demands an update of computational deletion mutation prediction. In this study, we deleted individually every residue of a small α-helical sterile alpha motif domain and investigated the structural and thermodynamic changes using 2D NMR spectroscopy and differential scanning fluorimetry. Then, we tested computational protocols to model and classify observed deletion mutants. We show a method using AlphaFold2 followed by RosettaRelax performs the best overall. In addition, a metric containing pLDDT values and Rosetta ΔΔG is most reliable in classifying tolerated deletion mutations. We further test this method on other datasets and show they hold for proteins known to harbor disease-causing deletion mutations.

Indexed as

Computational BiologyProteinsComputer SimulationMagnetic Resonance SpectroscopyMutationSequence DeletionProteinsAlphaFoldDeletionindelModelingmutationNMRRosettaSAM domainΔΔG

Identifiers

PMID37119820
PMCPMC10247520

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.