Evidence map›Paper›PMID 37368504›Full record

ArticleProtein science : a publication of the Protein Society2023

De novo design of stable proteins that efficaciously inhibit oncogenic G proteins.

Matthew C Cummins, Ashutosh Tripathy, John Sondek, Brian Kuhlman

Open access · bronzeAbstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.7field-weighted citation impact, top 29% of its field
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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Review
  2. Review
  3. De novo design of stable proteins that efficaciously inhibit oncogenic G proteins.Protein science : a publication of the Protein Society · 2023
    Article
4 · The record

Corrections and comments

  • Update of
    2023
5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Matthew C CumminsDepartment of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.ORCID 0000-0003-1119-4632
Ashutosh TripathyDepartment of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
John SondekDepartment of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
Brian KuhlmanDepartment of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.ORCID 0000-0003-4907-9699
University of North Carolina at Chapel Hill · US

Funding

Virology Research Program (Program 4)P30CA016086 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI David Darr · 1985 to 2026
$201.5M
GPU workstation for deep learning-based protein design and cryo-EM data processingR35GM131923 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BRIAN A KUHLMAN · 2019 to 2026
$6.1M
PREDOCTORAL TRAINING IN PHARMACOLOGICAL SCIST32GM007040 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI NICHOLAS, ROBERT A · 1985 to 2019
$6.0M
Phospholipase C IsozymesR35GM149299 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI JOHN E SONDEK · 2023 to 2026
$1.7M
Inhibition of GTPases and G proteins to treat human diseaseR01GM120291 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI LIU, RIHE, SONDEK, JOHN E · 2016 to 2019
$1.4M
NCI NIH HHS P30 CA016086NIGMS NIH HHS R01 GM120291NIGMS NIH HHS R01GM120291NIGMS NIH HHS R35 GM131923NIGMS NIH HHS R35GM131923NIGMS NIH HHS R35 GM149299NIGMS NIH HHS T32 GM007040NIGMS NIH HHS T32GM007040
6 · The paper itself

Abstract

Many protein therapeutics are competitive inhibitors that function by binding to endogenous proteins and preventing them from interacting with native partners. One effective strategy for engineering competitive inhibitors is to graft structural motifs from a native partner into a host protein. Here, we develop and experimentally test a computational protocol for embedding binding motifs in de novo designed proteins. The protocol uses an "inside-out" approach: Starting with a structural model of the binding motif docked against the target protein, the de novo protein is built by growing new structural elements off the termini of the binding motif. During backbone assembly, a score function favors backbones that introduce new tertiary contacts within the designed protein and do not introduce clashes with the target binding partner. Final sequences are designed and optimized using the molecular modeling program Rosetta. To test our protocol, we designed small helical proteins to inhibit the interaction between Gα

Indexed as

GTP-Binding ProteinsIsoenzymesModels, MolecularProtein BindingProtein EngineeringGTP-Binding ProteinsIsoenzymescomputational protein designde novo protein designG proteinsRosetta molecular modeling program

Identifiers

PMID37368504
PMCPMC10360382
OpenAlexW4382240329

What OpenQuestion holds

Textmetadata
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.