Evidence map›Paper›PMID 31754004›Full record

ArticleScience (New York, N.Y.)2019

Computational design of a modular protein sense-response system.

Anum A Glasgow, Yao-Ming Huang, Daniel J Mandell, Michael Thompson, Ryan Ritterson, Amanda L Loshbaugh, Jenna Pellegrino, Cody Krivacic, Roland A Pache, Kyle A Barlow and 5 more

Abstract read
In one paragraph

Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing 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

65 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Unusually broad-spectrum small-molecule sensing using a single protein scaffold.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  13. Protein A-like peptide generation based on generalized diffusion model.Journal of computer-aided molecular design · 2025
    Article
  14. Article
  15. De Novo Design of High-Performance Cortisol Luminescent Biosensors.Journal of the American Chemical Society · 2025
    Article
  16. A Designed ZnJournal of the American Chemical Society · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Efficient Generation of Protein Pockets with PocketGen.bioRxiv : the preprint server for biology · 2024
    Article

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors.

Anum A Glasgow *Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-0938-881X
Yao-Ming Huang *Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3583-3603
Daniel J Mandell *Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Michael ThompsonDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-6099-2027
Ryan RittersonDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-1284-8709
Amanda L LoshbaughDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7099-2832
Jenna PellegrinoDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
Cody KrivacicDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0001-8203-4762
Roland A PacheDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-4723-6729
Kyle A BarlowDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-9787-0066
Noah OllikainenDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-1174-2400
Deborah JeonDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-2724-6057
Mark J S KellyDepartment of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0003-3209-1018
James S FraserDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.ORCID 0000-0002-5080-2859
Tanja KortemmeDepartment of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA. tanjakortemme@gmail.com.ORCID 0000-0002-8494-680X

Funding

UCSF IRACDA Scholars ProgramK12GM081266 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Raymond M. Esquerra, HOLLY A. INGRAHAM · 2007 to 2026
$19.4M
STRUCTURAL BIOLOGY TRAINING PROGRAMT32GM008284 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 1988 to 2022
$10.1M
Computational design of protein-based small-molecule biosensorsR01GM110089 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 2015 to 2022
$2.3M
Computational design of protein-based modular small-molecule biosensorsR21EB013389 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KORTEMME, TANJA · 2011 to 2012
$425k
NIBIB NIH HHS R21 EB013389NIGMS NIH HHS K12 GM081266NIGMS NIH HHS R01 GM110089NIGMS NIH HHS T32 GM008284
6 · The paper itself

Abstract

Sensing and responding to signals is a fundamental ability of living systems, but despite substantial progress in the computational design of new protein structures, there is no general approach for engineering arbitrary new protein sensors. Here, we describe a generalizable computational strategy for designing sensor-actuator proteins by building binding sites de novo into heterodimeric protein-protein interfaces and coupling ligand sensing to modular actuation through split reporters. Using this approach, we designed protein sensors that respond to farnesyl pyrophosphate, a metabolic intermediate in the production of valuable compounds. The sensors are functional in vitro and in cells, and the crystal structure of the engineered binding site closely matches the design model. Our computational design strategy opens broad avenues to link biological outputs to new signals.

Indexed as

Protein EngineeringProtein MultimerizationAnkyrin RepeatBinding SitesBiosensing TechniquesComputational BiologyComputer SimulationCrystallography, X-RayLigandsMaltose-Binding ProteinsModels, MolecularPolyisoprenyl PhosphatesProteinsSesquiterpenesfarnesyl pyrophosphateLigandsMaltose-Binding ProteinsPolyisoprenyl PhosphatesProteinsSesquiterpenes

Identifiers

PMID31754004
PMCPMC7343396

What OpenQuestion holds

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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.