Evidence map›Paper›PMID 34785644›Full record

ArticleNature communications2021

Two-input protein logic gate for computation in living cells.

Yashavantha L Vishweshwaraiah, Jiaxing Chen, Venkat R Chirasani, Erdem D Tabdanov, Nikolay V Dokholyan

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.8field-weighted citation impact, top 8% 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

24 citing papers in PubMed, 55 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Review
  5. Review
  6. Optogenetic enzymes: A deep dive into design and impact.Current opinion in structural biology · 2025
    Review
  7. Article
  8. Review
  9. Review
  10. Protein design accelerates the development and application of optogenetic tools.Computational and structural biotechnology journal · 2025
    Review
  11. Optogenetically engineered Septin-7 enhances immune cell infiltration of tumor spheroids.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Allosteric regulation of kinase activity in living cells.bioRxiv : the preprint server for biology · 2023
    Article
  18. Article
  19. Allosteric inactivation of an engineered optogenetic GTPase.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  20. Catalyst-based biomolecular logic gates.Catalysts (Basel, Switzerland) · 2022
    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

5 authors at 2 institutions in 1 country.

Yashavantha L VishweshwaraiahDepartments of Pharmacology, Penn State College of Medicine, Hershey, PA, 17033-0850, USA.
Jiaxing ChenDepartments of Pharmacology, Penn State College of Medicine, Hershey, PA, 17033-0850, USA.ORCID 0000-0003-0150-1387
Venkat R ChirasaniDepartments of Pharmacology, Penn State College of Medicine, Hershey, PA, 17033-0850, USA.ORCID 0000-0003-1416-0438
Erdem D TabdanovDepartments of Pharmacology, Penn State College of Medicine, Hershey, PA, 17033-0850, USA.ORCID 0000-0003-2673-112X
Nikolay V DokholyanDepartments of Pharmacology, Penn State College of Medicine, Hershey, PA, 17033-0850, USA. dokh@psu.edu.ORCID 0000-0002-8225-4025
Penn State Milton S. Hershey Medical Center · USPennsylvania State University · US

Funding

Nanoscale programming of cellular and physiological phenotypes: EquipmentR35GM134864 · NIGMS · UNIVERSITY OF VIRGINIA · PI Nikolay Dokholyan · 2020 to 2026
$5.2M
NIGMS NIH HHS R35 GM134864
6 · The paper itself

Abstract

Advances in protein design have brought us within reach of developing a nanoscale programming language, in which molecules serve as operands and their conformational states function as logic gates with precise input and output behaviors. Combining these nanoscale computing agents into larger molecules and molecular complexes will allow us to write and execute "code". Here, in an important step toward this goal, we report an engineered, single protein design that is allosterically regulated to function as a 'two-input logic OR gate'. Our system is based on chemo- and optogenetic regulation of focal adhesion kinase. In the engineered FAK, all of FAK domain architecture is retained and key intramolecular interactions between the kinase and the FERM domains are externally controlled through a rapamycin-inducible uniRapR module in the kinase domain and a light-inducible LOV2 module in the FERM domain. Orthogonal regulation of protein function was possible using the chemo- and optogenetic switches. We demonstrate that dynamic FAK activation profoundly increased cell multiaxial complexity in the fibrous extracellular matrix microenvironment and decreased cell motility. This work provides proof-of-principle for fine multimodal control of protein function and paves the way for construction of complex nanoscale computing agents.

Indexed as

Computational BiologyProteinsSynthetic BiologyCell MovementFibroblastsFocal Adhesion Protein-Tyrosine KinasesHeLa CellsHumansFocal Adhesion Protein-Tyrosine KinasesProteins

Identifiers

PMID34785644
PMCPMC8595391
OpenAlexW3213531472

What Socratic 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 Socratic graph.