Evidence map›Paper›PMID 37790440›Full record

ArticlebioRxiv : the preprint server for biology2023

Computational design of sequence-specific DNA-binding proteins.

Cameron J Glasscock, Robert Pecoraro, Ryan McHugh, Lindsey A Doyle, Wei Chen, Olivier Boivin, Beau Lonnquist, Emily Na, Yuliya Politanska, Hugh K Haddox and 10 more

Open access · greenAbstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed, 27 citations in OpenAlex.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 2 countries.

Cameron J GlasscockDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Robert PecoraroDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Ryan McHughDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Lindsey A DoyleDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Wei ChenDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Olivier BoivinProgram in Genetics and Genomic, Duke University, Durham, NC, USA.
Beau LonnquistDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Emily NaDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Yuliya PolitanskaDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Hugh K HaddoxDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
David CoxDepartment of Biochemistry, Stanford University School of Medicine, Palo Alto, CA USA.
Christoffer NornDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Brian CoventryDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Inna GoreshnikDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Dionne VafeadosDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Gyu Rie LeeDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Raluca GordanCenter for Advanced Genomic Technologies, Duke University, Durham, NC, USA.
Barry L StoddardDivision of Basic Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Frank DiMaioDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
David BakerDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
University of Washington · USFred Hutch Cancer Center · USDuke University · USHoward Hughes Medical Institute · USStanford University · US

Funding

User Training and OutreachP30GM124169 · NIGMS · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI Gregory L Hura · 2017 to 2026
$28.6M
The role of transcription factor proteins in mutagenesis at regulatory sitesR01GM135658 · NIGMS · DUKE UNIVERSITY · PI GORDAN, RALUCA · 2020 to 2023
$1.3M
Pilatus 6mS10OD021832 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI ADAMS, PAUL DAVID · 2016 to 2016
$980k
Acquisition of a Rigaku XtaLAB Synergy-R macromolecular diffraction instrumentation at Fred Hutchinson Cancer Research CenterS10OD028581 · OD · FRED HUTCHINSON CANCER RESEARCH CENTER · PI STODDARD, BARRY L. · 2020 to 2020
$600k
NIGMS NIH HHS P30 GM124169NIGMS NIH HHS R01 GM135658NIH HHS S10 OD021832NIH HHS S10 OD028581
6 · The paper itself

Abstract

Sequence-specific DNA-binding proteins (DBPs) play critical roles in biology and biotechnology, and there has been considerable interest in the engineering of DBPs with new or altered specificities for genome editing and other applications. While there has been some success in reprogramming naturally occurring DBPs using selection methods, the computational design of new DBPs that recognize arbitrary target sites remains an outstanding challenge. We describe a computational method for the design of small DBPs that recognize specific target sequences through interactions with bases in the major groove, and employ this method in conjunction with experimental screening to generate binders for 5 distinct DNA targets. These binders exhibit specificity closely matching the computational models for the target DNA sequences at as many as 6 base positions and affinities as low as 30-100 nM. The crystal structure of a designed DBP-target site complex is in close agreement with the design model, highlighting the accuracy of the design method. The designed DBPs function in both

Identifiers

PMID37790440
PMCPMC10542524
OpenAlexW4386965027

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.