Evidence map›Paper›PMID 27805033›Full record

ArticleScientific reports2016

Identification of DNA primase inhibitors via a combined fragment-based and virtual screening.

Stefan Ilic, Sabine R Akabayov, Haribabu Arthanari, Gerhard Wagner, Charles C Richardson, Barak Akabayov

Abstract read
In one paragraph

Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Key Topics in Molecular Docking for Drug Design.International journal of molecular sciences · 2019
    Review
  7. Review
  8. NMR-Fragment Based Virtual Screening: A Brief Overview.Molecules (Basel, Switzerland) · 2018
    Review
  9. 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

6 authors.

Stefan IlicDepartment of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
Sabine R AkabayovDepartment of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.
Haribabu ArthanariDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave., Boston, Massachusetts 02115, USA.
Gerhard WagnerDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave., Boston, Massachusetts 02115, USA.
Charles C RichardsonDepartment of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Ave., Boston, Massachusetts 02115, USA.
Barak AkabayovDepartment of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, 8410501, Israel.

Funding

T CELL SPECIFIC TRANSCRIPTION COMPLEXESP01GM047467 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAGNER, GERHARD · 1992 to 2017
$28.6M
STRUCTURAL BASIS OF TRANSLATION INITIATION BY EIF-4ER01CA068262 · NCI · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WAGNER, GERHARD · 1996 to 2015
$3.6M
NCI NIH HHS R01 CA068262NIGMS NIH HHS P01 GM047467
6 · The paper itself

Abstract

The structural differences between bacterial and human primases render the former an excellent target for drug design. Here we describe a technique for selecting small molecule inhibitors of the activity of T7 DNA primase, an ideal model for bacterial primases due to their common structural and functional features. Using NMR screening, fragment molecules that bind T7 primase were identified and then exploited in virtual filtration to select larger molecules from the ZINC database. The molecules were docked to the primase active site using the available primase crystal structure and ranked based on their predicted binding energies to identify the best candidates for functional and structural investigations. Biochemical assays revealed that some of the molecules inhibit T7 primase-dependent DNA replication. The binding mechanism was delineated via NMR spectroscopy. Our approach, which combines fragment based and virtual screening, is rapid and cost effective and can be applied to other targets.

Indexed as

Bacteriophage T7Catalytic DomainCrystallography, X-RayDNA PrimaseDNA ReplicationEnzyme InhibitorsHumansModels, MolecularMolecular Docking SimulationNuclear Magnetic Resonance, BiomolecularSmall Molecule LibrariesViral ProteinsDNA PrimaseEnzyme InhibitorsSmall Molecule LibrariesViral Proteins

Identifiers

PMID27805033
PMCPMC5090872

What OpenQuestion holds

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LicenceCC BY
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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.