Evidence map›Paper›PMID 33582133›Full record

ArticleBiophysical journal2021

A predictive coarse-grained model for position-specific effects of post-translational modifications.

Theodora Myrto Perdikari, Nina Jovic, Gregory L Dignon, Young C Kim, Nicolas L Fawzi, Jeetain Mittal

Open access · bronzeAbstract read
In one paragraph

Article in Biophysical journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
5.2field-weighted citation impact, top 3% 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

49 citing papers in PubMed, 81 citations in OpenAlex.

  1. Review
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  5. Phosphorylation event changes the RNA binding mode of EZH2 disordered segment.Protein science : a publication of the Protein Society · 2026
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  20. Phosphorylation sites are evolutionary checkpoints against liquid-solid transition in protein condensates.Proceedings of the National Academy of Sciences of the United States of America · 2023
    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

6 authors at 4 institutions in 1 country.

Theodora Myrto PerdikariCenter for Biomedical Engineering, Brown University, Providence, Rhode Island.
Nina JovicDepartment of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania.
Gregory L DignonDepartment of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania; Laufer Center for Physical and Quantitative Biology, Stony Brook University, Stony Brook, New York.
Young C KimCenter for Materials Physics and Technology, U.S. Naval Research Laboratory, Washington D.C.
Nicolas L FawziDepartment of Molecular Pharmacology, Physiology, and Biotechnology; Robert J. and Nancy D. Carney Institute for Brain Science, Brown University, Providence, Rhode Island. Electronic address: nicolas_fawzi@brown.edu.
Jeetain MittalDepartment of Chemical and Biomolecular Engineering, Lehigh University, Bethlehem, Pennsylvania. Electronic address: jeetain@lehigh.edu.
Lehigh University · USAllen Institute for Brain Science · USBrown University · USUnited States Naval Research Laboratory · US

Funding

Functional and Pathological Interactions of TDP-43R01NS116176 · NINDS · BROWN UNIVERSITY · PI FAWZI, NICOLAS LUX, MITTAL, JEETAIN · 2020 to 2024
$3.6M
Turning off the molecular switch for pathological self-assembly of FUSR01GM118530 · NIGMS · BROWN UNIVERSITY · PI FAWZI, NICOLAS LUX · 2016 to 2020
$1.6M
Liquid-Liquid Phase Separation in Heterochromatin OrganizationR01GM136917 · NIGMS · TEXAS ENGINEERING EXPERIMENT STATION · PI MITTAL, JEETAIN · 2020 to 2023
$1.4M
NIGMS NIH HHS R01 GM118530NIGMS NIH HHS R01 GM136917NINDS NIH HHS R01 NS116176
6 · The paper itself

Abstract

Biomolecules undergo liquid-liquid phase separation (LLPS), resulting in the formation of multicomponent protein-RNA membraneless organelles in cells. However, the physiological and pathological role of post-translational modifications (PTMs) on the biophysics of phase behavior is only beginning to be probed. To study the effect of PTMs on LLPS in silico, we extend our transferable coarse-grained model of intrinsically disordered proteins to include phosphorylated and acetylated amino acids. Using the parameters for modified amino acids available for fixed-charge atomistic force fields, we parameterize the size and atomistic hydropathy of the coarse-grained-modified amino acid beads and, hence, the interactions between the modified and natural amino acids. We then elucidate how the number and position of phosphorylated and acetylated residues alter the protein's single-chain compactness and its propensity to phase separate. We show that both the number and the position of phosphorylated threonines/serines or acetylated lysines can serve as a molecular on/off switch for phase separation in the well-studied disordered regions of Fused in Sarcoma (FUS) and DDX3X, respectively. We also compare modified residues to their commonly used PTM mimics for their impact on chain properties. Importantly, we show that the model can predict and capture experimentally measured differences in the phase behavior for position-specific modifications, showing that the position of modifications can dictate phase separation. In sum, this model will be useful for studying LLPS of post-translationally modified intrinsically disordered proteins and predicting how modifications control phase behavior with position-specific resolution.

Indexed as

Intrinsically Disordered ProteinsComputer SimulationOrganellesProtein Processing, Post-TranslationalIntrinsically Disordered Proteins

Identifiers

PMID33582133
PMCPMC8059201
OpenAlexW3132553925

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.