Evidence map›Paper›PMID 31451655›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2019

Predictive shifts in free energy couple mutations to their phenotypic consequences.

Griffin Chure, Manuel Razo-Mejia, Nathan M Belliveau, Tal Einav, Zofii A Kaczmarek, Stephanie L Barnes, Mitchell Lewis, Rob Phillips

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. 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
4.3field-weighted citation impact, top 6% 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, 46 citations in OpenAlex.

  1. Article
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  4. The Environment-Dependent Regulatory Landscape of thebioRxiv : the preprint server for biology · 2025
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  12. Interpretable modeling of genotype-phenotype landscapes with state-of-the-art predictive power.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Functional plasticity and evolutionary adaptation of allosteric regulation.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  18. Article
  19. Article
  20. Predictive shifts in free energy couple mutations to their phenotypic consequences.Proceedings of the National Academy of Sciences of the United States of America · 2019
    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

8 authors at 2 institutions in 1 country.

Griffin ChureDepartment of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.ORCID 0000-0002-2216-2057
Manuel Razo-MejiaDepartment of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Nathan M BelliveauDepartment of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.ORCID 0000-0002-1536-1963
Tal EinavDepartment of Physics, California Institute of Technology, Pasadena, CA 91125.ORCID 0000-0003-0777-1193
Zofii A KaczmarekDepartment of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Stephanie L BarnesDepartment of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
Mitchell LewisDepartment of Biochemistry and Molecular Biophysics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104.
Rob PhillipsDepartment of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125; phillips@pboc.caltech.edu.ORCID 0000-0003-3082-2809
California Institute of Technology · USUniversity of Pennsylvania · US

Funding

The Principles of Regulatory, Conformational and Evolutionary AdaptationR35GM118043 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI ROB PHILLIPS · 2016 to 2026
$7.9M
NIH Director's Pioneer Award (RMI)DP1OD000217 · OD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI PHILLIPS, ROB · 2004 to 2008
$4.0M
Single-Molecule and Single-Cell Analysis of Transcription Factor-DNA ComplexesR01GM085286 · NIGMS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI PHILLIPS, ROB · 2009 to 2015
$2.8M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM085286NIGMS NIH HHS R35 GM118043NIH HHS DP1 OD000217
6 · The paper itself

Abstract

Mutation is a critical mechanism by which evolution explores the functional landscape of proteins. Despite our ability to experimentally inflict mutations at will, it remains difficult to link sequence-level perturbations to systems-level responses. Here, we present a framework centered on measuring changes in the free energy of the system to link individual mutations in an allosteric transcriptional repressor to the parameters which govern its response. We find that the energetic effects of the mutations can be categorized into several classes which have characteristic curves as a function of the inducer concentration. We experimentally test these diagnostic predictions using the well-characterized LacI repressor of

Indexed as

Genetic Association StudiesModels, BiologicalMutationPhenotypeAlgorithmsAllosteric RegulationDNA-Binding ProteinsEnergy MetabolismEscherichia coliGene DosageLac RepressorsOperator Regions, GeneticProtein Interaction Domains and MotifsDNA-Binding ProteinsLac Repressorsallosterybiophysicsmutationstatistical mechanicstranscriptional regulation

Identifiers

PMID31451655
PMCPMC6744869
OpenAlexW2971141280

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.