Evidence map›Paper›PMID 36599844›Full record

ArticleNature communications2023

Tuning phenylalanine fluorination to assess aromatic contributions to protein function and stability in cells.

Grace D Galles, Daniel T Infield, Colin J Clark, Marcus L Hemshorn, Shivani Manikandan, Frederico Fazan, Ali Rasouli, Emad Tajkhorshid, Jason D Galpin, Richard B Cooley and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

20 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
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  4. Chemical tuning reveals a cation-π gating bridge between the voltage-sensor and pore domains in the KProceedings of the National Academy of Sciences of the United States of America · 2026
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  8. Leveraging relaxation-optimizedNature chemistry · 2025
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  9. Rational design ofNature communications · 2025
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  15. Review
  16. Contribution of Electrostatic CHJournal of the American Chemical Society · 2024
    Article
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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

12 authors at 3 institutions in 1 country.

Grace D Galles *Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, USA.ORCID http://orcid.org/0000-0002-8058-9526
Daniel T Infield *Department of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, USA.
Colin J ClarkDepartment of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, USA.
Marcus L HemshornThe GCE4All Research Center, Department of Biochemistry & Biophysics, Oregon State University, Corvallis, OR, USA.
Shivani ManikandanDepartment of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, USA.ORCID http://orcid.org/0000-0001-5193-7950
Frederico FazanDepartment of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, USA.
Ali RasouliTheoretical and Computational Biophysics Group, NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0002-0313-0236
Emad TajkhorshidTheoretical and Computational Biophysics Group, NIH Center for Macromolecular Modeling and Bioinformatics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.ORCID http://orcid.org/0000-0001-8434-1010
Jason D GalpinDepartment of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, USA.ORCID http://orcid.org/0000-0003-1923-5312
Richard B CooleyThe GCE4All Research Center, Department of Biochemistry & Biophysics, Oregon State University, Corvallis, OR, USA.
Ryan A MehlThe GCE4All Research Center, Department of Biochemistry & Biophysics, Oregon State University, Corvallis, OR, USA.
Christopher A AhernDepartment of Molecular Physiology and Biophysics, University of Iowa College of Medicine, Iowa City, IA, USA. christopher-ahern@uiowa.edu.ORCID http://orcid.org/0000-0002-7975-2744
University of Iowa · USOregon State University · USUniversity of Illinois Urbana-Champaign · US

Funding

WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI TAJKHORSHID, EMAD · 2012 to 2021
$19.0M
Resource for Macromolecular Modeling and VisualizationR24GM145965 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Emad Tajkhorshid · 2022 to 2026
$6.2M
The GCE4All Center: Unleashing the Potential of Genetic Code Expansion for Biomedical ResearchRM1GM144227 · NIGMS · OREGON STATE UNIVERSITY · PI RYAN A MEHL · 2022 to 2026
$6.2M
Toolkit for High-Resolution Structure and Dynamics of Functional LipidsR01GM123455 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI MORRISSEY, JAMES H., RIENSTRA, CHAD M · 2016 to 2020
$5.0M
Chemical biology of voltage-gated cation channelsR35GM148239 · NIGMS · UNIVERSITY OF IOWA · PI Christopher A Ahern · 2023 to 2026
$2.5M
Photochemical determination of sodium channel voltage-dependent gating and compositionR01GM122420 · NIGMS · UNIVERSITY OF IOWA · PI AHERN, CHRISTOPHER A · 2017 to 2020
$1.5M
Atomic basis for chloride channel and transporter gating and selectivityR01GM128420 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI ACCARDI, ALESSIO · 2019 to 2022
$1.5M
Development of an improved core technology for efficient genetic code expansion in biomedical researchR01GM131168 · NIGMS · OREGON STATE UNIVERSITY · PI MEHL, RYAN A · 2019 to 2021
$1.1M
The Facility for Atomic MutagenesisR24NS104617 · NINDS · UNIVERSITY OF IOWA · PI AHERN, CHRISTOPHER A · 2018 to 2021
$1.0M
NIGMS NIH HHS P41 GM104601NIGMS NIH HHS R01 GM122420NIGMS NIH HHS R01 GM123455NIGMS NIH HHS R01 GM128420NIGMS NIH HHS R01 GM131168NIGMS NIH HHS R24 GM145965NIGMS NIH HHS R35 GM148239NIGMS NIH HHS RM1 GM144227NINDS NIH HHS R24 NS104617
6 · The paper itself

Abstract

The aromatic side-chains of phenylalanine, tyrosine, and tryptophan interact with their environments via both hydrophobic and electrostatic interactions. Determining the extent to which these contribute to protein function and stability is not possible with conventional mutagenesis. Serial fluorination of a given aromatic is a validated method in vitro and in silico to specifically alter electrostatic characteristics, but this approach is restricted to a select few experimental systems. Here, we report a group of pyrrolysine-based aminoacyl-tRNA synthetase/tRNA pairs (tRNA/RS pairs) that enable the site-specific encoding of a varied spectrum of fluorinated phenylalanine amino acids in E. coli and mammalian (HEK 293T) cells. By allowing the cross-kingdom expression of proteins bearing these unnatural amino acids at biochemical scale, these tools may potentially enable the study of biological mechanisms which utilize aromatic interactions in structural and cellular contexts.

Indexed as

Amino Acyl-tRNA SynthetasesPhenylalanineAmino AcidsEscherichia coliHalogenationHEK293 CellsHumansRNA, TransferAmino AcidsAmino Acyl-tRNA SynthetasesPhenylalanineRNA, Transfer

Identifiers

PMID36599844
PMCPMC9813137
OpenAlexW4313545430

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.