Evidence mapPaperPMID 42200482Full record

ArticleProtein science : a publication of the Protein Society2026

ERK autoinhibition mechanism informs a drug combination strategy.

Clil Regev, Hyunbum Jang, Ruth Nussinov

Abstract read
In one paragraph

Article in Protein science : a publication of the Protein Society, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. ERK autoinhibition mechanism informs a drug combination strategy.Protein science : a publication of the Protein Society · 2026
    Article
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

3 authors.

Clil RegevCancer Innovation Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, USA.ORCID https://orcid.org/0000-0001-9879-1936
Hyunbum JangCancer Innovation Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, USA.ORCID https://orcid.org/0000-0001-9402-4051
Ruth NussinovCancer Innovation Laboratory, National Cancer Institute at Frederick, Frederick, Maryland, USA.ORCID https://orcid.org/0000-0002-8115-6415

Funding

NCI NIH HHS HHSN261201500003I
6 · The paper itself

Abstract

ERK is a key regulator in the MAPK pathway, controlling essential cell processes through dual-phosphorylation-based activation. We investigate the conformational equilibrium between inactive and active ERK states, which is controlled allosterically by its structurally unique C-terminal L16 segment. Using molecular dynamics simulations of full-length and truncated ERK variants across phosphorylation states, we demonstrate that activation is achieved through a lateral αC-helix rotation initiated by dual-phosphorylation. The L16 segment intrinsically stabilizes the inactive kinase conformation by restricting αC-helix orientation, counteracting its natural tendency to adopt an active alignment. Removal of the L16 loop disrupts the unphosphorylated state, whereas all phosphorylated systems remain stable. The α

Indexed as

Mitogen-Activated Protein Kinase 1Protein Kinase InhibitorsAllosteric RegulationHumansMolecular Dynamics SimulationPhosphorylationMitogen-Activated Protein Kinase 1Protein Kinase Inhibitorsallosteryautoinhibitioncombination therapyERK2L16 segmentmolecular dynamics

Identifiers

PMID42200482
PMCPMC13240268

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.