Evidence map›Paper›PMID 27425410›Full record

ArticleMolecular cell2016

Automated Structure- and Sequence-Based Design of Proteins for High Bacterial Expression and Stability.

Adi Goldenzweig, Moshe Goldsmith, Shannon E Hill, Or Gertman, Paola Laurino, Yacov Ashani, Orly Dym, Tamar Unger, Shira Albeck, Jaime Prilusky and 6 more

Erratum issuedOpen access · hybridAbstract read
In one paragraph

Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 264 papers.

0numbers the graph read from it
0cells of the map it votes in
264citing papers in PubMed
32.2field-weighted citation impact, top 1% 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

264 citing papers in PubMed, 555 citations in OpenAlex.

  1. Review
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  7. Chemical Biology 2025: Highlights From the Ch/Bi145 Course at Caltech.Chembiochem : a European journal of chemical biology · 2026
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  11. Empowering Precision C-H Functionalization: Advances in Peroxygenase Engineering.Angewandte Chemie (International ed. in English) · 2026
    Review
  12. Article
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  14. Review
  15. Article
  16. Multicyclic D-Stereospecific Hydrolase Dimer With High Sustained Activity.Angewandte Chemie (International ed. in English) · 2026
    Article
  17. Article
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  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Adi GoldenzweigDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Moshe GoldsmithDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Shannon E HillSchool of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
Or GertmanDepartment of Life Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel.
Paola LaurinoDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel.
Yacov AshaniDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel; Israel Structural Proteomics Center, Weizmann Institute of Science, Rehovot 7610001, Israel.
Orly DymIsrael Structural Proteomics Center, Weizmann Institute of Science, Rehovot 7610001, Israel.
Tamar UngerIsrael Structural Proteomics Center, Weizmann Institute of Science, Rehovot 7610001, Israel.
Shira AlbeckIsrael Structural Proteomics Center, Weizmann Institute of Science, Rehovot 7610001, Israel.
Jaime PriluskyBioinformatics & Biological Computing Unit, Weizmann Institute of Science, Rehovot 7610001, Israel.
Raquel L LiebermanSchool of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
Amir AharoniDepartment of Life Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel.
Israel SilmanDepartment of Neurobiology, Weizmann Institute of Science, Rehovot 7610001, Israel.
Joel L SussmanIsrael Structural Proteomics Center, Weizmann Institute of Science, Rehovot 7610001, Israel.
Dan S TawfikDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: dan.tawfik@weizmann.ac.il.
Sarel J FleishmanDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: sarel@weizmann.ac.il.
Weizmann Institute of Science · ILBen-Gurion University of the Negev · ILGeorgia Institute of Technology · US

Funding

Request for Supplement to Promote Diversity in Health Related ResearchR01EY021205 · NEI · GEORGIA INSTITUTE OF TECHNOLOGY · PI Raquel L Lieberman · 2011 to 2026
$6.8M
NEI NIH HHS R01 EY021205
6 · The paper itself

Abstract

Upon heterologous overexpression, many proteins misfold or aggregate, thus resulting in low functional yields. Human acetylcholinesterase (hAChE), an enzyme mediating synaptic transmission, is a typical case of a human protein that necessitates mammalian systems to obtain functional expression. We developed a computational strategy and designed an AChE variant bearing 51 mutations that improved core packing, surface polarity, and backbone rigidity. This variant expressed at ∼2,000-fold higher levels in E. coli compared to wild-type hAChE and exhibited 20°C higher thermostability with no change in enzymatic properties or in the active-site configuration as determined by crystallography. To demonstrate broad utility, we similarly designed four other human and bacterial proteins. Testing at most three designs per protein, we obtained enhanced stability and/or higher yields of soluble and active protein in E. coli. Our algorithm requires only a 3D structure and several dozen sequences of naturally occurring homologs, and is available at http://pross.weizmann.ac.il.

Indexed as

AcetylcholinesteraseAlgorithmsAutomation, LaboratoryComputational BiologyComputer-Aided DesignComputer SimulationDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3AEscherichia coliGene Expression Regulation, BacterialGene Expression Regulation, EnzymologicGPI-Linked ProteinsMutationPhosphoric Triester HydrolasesProtein ConformationProtein DenaturationAcetylcholinesteraseACHE protein, humanDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanGPI-Linked ProteinsPhosphoric Triester HydrolasesSIRT6 protein, humanSirtuins

Identifiers

PMID27425410
PMCPMC4961223
OpenAlexW2473135273

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.