Evidence map›Paper›PMID 27503953›Full record

ArticleProtein engineering, design & selection : PEDS2016

GADIS: Algorithm for designing sequences to achieve target secondary structure profiles of intrinsically disordered proteins.

Tyler S Harmon, Michael D Crabtree, Sarah L Shammas, Ammon E Posey, Jane Clarke, Rohit V Pappu

Abstract read
In one paragraph

Article in Protein engineering, design & selection : PEDS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

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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

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2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Review
  2. Article
  3. Structural biases in disordered proteins are prevalent in the cell.Nature structural & molecular biology · 2024
    Article
  4. Article
  5. Dilute phase oligomerization can oppose phase separation and modulate material properties of a ribonucleoprotein condensate.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. InSiDDe: A Server for Designing Artificial Disordered Proteins.International journal of molecular sciences · 2017
    Article
  14. Article
  15. Article
4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

6 authors.

Tyler S HarmonDepartment of Physics, Washington University in St. Louis, St. Louis, MO 63130, USA Department of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA.
Michael D CrabtreeDepartment of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK.
Sarah L ShammasDepartment of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK.
Ammon E PoseyDepartment of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA.
Jane ClarkeDepartment of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, UK.
Rohit V PappuDepartment of Biomedical Engineering and Center for Biological Systems Engineering, Washington University in St. Louis, St. Louis, MO 63130, USA pappu@wustl.edu.

Funding

Biotechnology and Biological Sciences Research CouncilMedical Research Council MC_U105485808Wellcome Trust WT 095195MA
6 · The paper itself

Abstract

Many intrinsically disordered proteins (IDPs) participate in coupled folding and binding reactions and form alpha helical structures in their bound complexes. Alanine, glycine, or proline scanning mutagenesis approaches are often used to dissect the contributions of intrinsic helicities to coupled folding and binding. These experiments can yield confounding results because the mutagenesis strategy changes the amino acid compositions of IDPs. Therefore, an important next step in mutagenesis-based approaches to mechanistic studies of coupled folding and binding is the design of sequences that satisfy three major constraints. These are (i) achieving a target intrinsic alpha helicity profile; (ii) fixing the positions of residues corresponding to the binding interface; and (iii) maintaining the native amino acid composition. Here, we report the development of a G: enetic A: lgorithm for D: esign of I: ntrinsic secondary S: tructure (GADIS) for designing sequences that satisfy the specified constraints. We describe the algorithm and present results to demonstrate the applicability of GADIS by designing sequence variants of the intrinsically disordered PUMA system that undergoes coupled folding and binding to Mcl-1. Our sequence designs span a range of intrinsic helicity profiles. The predicted variations in sequence-encoded mean helicities are tested against experimental measurements.

Indexed as

AlgorithmsAmino Acid SequenceIntrinsically Disordered ProteinsModels, MolecularMutagenesisProtein EngineeringProtein Structure, SecondaryIntrinsically Disordered ProteinsdesignGADISintrinsically disordered proteinsintrinsically helicity

Identifiers

PMID27503953
PMCPMC5001138

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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.