Evidence map›Paper›PMID 30531862›Full record

ArticleNature communications2018

Discovering de novo peptide substrates for enzymes using machine learning.

Lorillee Tallorin, JiaLei Wang, Woojoo E Kim, Swagat Sahu, Nicolas M Kosa, Pu Yang, Matthew Thompson, Michael K Gilson, Peter I Frazier, Michael D Burkart and 1 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

29 citing papers in PubMed, 82 citations in OpenAlex.

  1. Review
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  3. Review
  4. Article
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  6. Article
  7. Article
  8. Microbial synthesis of pyrroloquinoline quinone.World journal of microbiology & biotechnology · 2023
    Review
  9. Article
  10. Article
  11. Article
  12. Anti-Cancer Peptides: Status and Future Prospects.Molecules (Basel, Switzerland) · 2023
    Review
  13. Article
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. 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

11 authors at 3 institutions in 1 country.

Lorillee TallorinDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
JiaLei WangSchool of Operations Research and Information Engineering, Cornell University, 232 Rhodes Hall, Ithaca, NY, 14853-3801, USA.ORCID http://orcid.org/0000-0001-7556-4941
Woojoo E KimDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
Swagat SahuDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
Nicolas M KosaDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
Pu YangSchool of Operations Research and Information Engineering, Cornell University, 232 Rhodes Hall, Ithaca, NY, 14853-3801, USA.
Matthew ThompsonDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA.
Michael K GilsonSkaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.ORCID http://orcid.org/0000-0002-3375-1738
Peter I FrazierSchool of Operations Research and Information Engineering, Cornell University, 232 Rhodes Hall, Ithaca, NY, 14853-3801, USA. pf98@cornell.edu.
Michael D BurkartDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA. mburkart@ucsd.edu.ORCID http://orcid.org/0000-0002-4472-2254
Nathan C GianneschiDepartment of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0358, USA. nathan.gianneschi@northwestern.edu.ORCID http://orcid.org/0000-0001-9945-5475
University of California San Diego · USCornell University · USNorthwestern University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The discovery of peptide substrates for enzymes with exclusive, selective activities is a central goal in chemical biology. In this paper, we develop a hybrid computational and biochemical method to rapidly optimize peptides for specific, orthogonal biochemical functions. The method is an iterative machine learning process by which experimental data is deposited into a mathematical algorithm that selects potential peptide substrates to be tested experimentally. Once tested, the algorithm uses the experimental data to refine future selections. This process is repeated until a suitable set of de novo peptide substrates are discovered. We employed this technology to discover orthogonal peptide substrates for 4'-phosphopantetheinyl transferase, an enzyme class that covalently modifies proteins. In this manner, we have demonstrated that machine learning can be leveraged to guide peptide optimization for specific biochemical functions not immediately accessible by biological screening techniques, such as phage display and random mutagenesis.

Indexed as

Machine LearningAmino Acid SequenceBacterial ProteinsBayes TheoremPeptidesProtein BindingRecombinant ProteinsSubstrate SpecificityTransferases (Other Substituted Phosphate Groups)Bacterial ProteinsPeptidesphosphopantetheinyl transferaseRecombinant ProteinsTransferases (Other Substituted Phosphate Groups)

Identifiers

PMID30531862
PMCPMC6286390
OpenAlexW2903545365

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.