Evidence map›Paper›PMID 24816088›Full record

ArticleActa crystallographica. Section D, Biological crystallography2014

Hitting the target: fragment screening with acoustic in situ co-crystallization of proteins plus fragment libraries on pin-mounted data-collection micromeshes.

Xingyu Yin, Alexander Scalia, Ludmila Leroy, Christina M Cuttitta, Gina M Polizzo, Daniel L Ericson, Christian G Roessler, Olven Campos, Millie Y Ma, Rakhi Agarwal and 5 more

Abstract read
In one paragraph

Article in Acta crystallographica. Section D, Biological crystallography, 2014. 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
–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

24 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Serial crystallography with multi-stage merging of thousands of images.Acta crystallographica. Section F, Structural biology communications · 2022
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Strategies for sample delivery for femtosecond crystallography.Acta crystallographica. Section D, Structural biology · 2019
    Review
  12. Article
  13. Using sound pulses to solve the crystal-harvesting bottleneck.Acta crystallographica. Section D, Structural biology · 2018
    Article
  14. Article
  15. Gentle, fast and effective crystal soaking by acoustic dispensing.Acta crystallographica. Section D, Structural biology · 2017
    Article
  16. Article
  17. Article
  18. Automated harvesting and processing of protein crystals through laser photoablation.Acta crystallographica. Section D, Structural biology · 2016
    Article
  19. Article
  20. In meso in situ serial X-ray crystallography of soluble and membrane proteins.Acta crystallographica. Section D, Biological crystallography · 2015
    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

15 authors.

Xingyu YinOffice of Educational Programs, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Alexander ScaliaOffice of Educational Programs, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Ludmila LeroyOffice of Educational Programs, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Christina M CuttittaOffice of Educational Programs, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Gina M PolizzoOffice of Educational Programs, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Daniel L EricsonOffice of Educational Programs, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Christian G RoesslerPhoton Sciences Directorate, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Olven CamposOffice of Educational Programs, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Millie Y MaOffice of Educational Programs, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Rakhi AgarwalBiosciences Department, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Rick JackimowiczPhoton Sciences Directorate, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Marc AllairePhoton Sciences Directorate, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Allen M OrvillePhoton Sciences Directorate, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Robert M SweetPhoton Sciences Directorate, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.
Alexei S SoaresPhoton Sciences Directorate, Brookhaven National Laboratory, Upton, NY 11973-5000, USA.

Funding

X-RAY STRUCTURE OF RIFM PROTEIN FROM THE BIOSYNTHESIS PATHWAY OF THE ANSAMYCIN AP41RR012408 · NCRR · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI ORVILLE, ALLEN M · 1998 to 2011
$32.2M
Life Science and Biomedical technology Research center at NSLS-II LSBRP41GM111244 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI MCSWEENEY, SEAN · 2014 to 2018
$16.4M
Macromolecular Crystallography at the National Synchrotron Light SourceP41GM103473 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI SWEET, ROBERT M · 2012 to 2013
$4.9M
NCRR NIH HHS P41 RR012408NIGMS NIH HHS P41 GM103473NIGMS NIH HHS P41 GM111244
6 · The paper itself

Abstract

Acoustic droplet ejection (ADE) is a powerful technology that supports crystallographic applications such as growing, improving and manipulating protein crystals. A fragment-screening strategy is described that uses ADE to co-crystallize proteins with fragment libraries directly on MiTeGen MicroMeshes. Co-crystallization trials can be prepared rapidly and economically. The high speed of specimen preparation and the low consumption of fragment and protein allow the use of individual rather than pooled fragments. The Echo 550 liquid-handling instrument (Labcyte Inc., Sunnyvale, California, USA) generates droplets with accurate trajectories, which allows multiple co-crystallization experiments to be discretely positioned on a single data-collection micromesh. This accuracy also allows all components to be transferred through small apertures. Consequently, the crystallization tray is in equilibrium with the reservoir before, during and after the transfer of protein, precipitant and fragment to the micromesh on which crystallization will occur. This strict control of the specimen environment means that the crystallography experiments remain identical as the working volumes are decreased from the few microlitres level to the few nanolitres level. Using this system, lysozyme, thermolysin, trypsin and stachydrine demethylase crystals were co-crystallized with a small 33-compound mini-library to search for fragment hits. This technology pushes towards a much faster, more automated and more flexible strategy for structure-based drug discovery using as little as 2.5 nl of each major component.

Indexed as

AcousticsSmall Molecule LibrariesCrystallizationCrystallography, X-RayDrug DiscoveryEquipment DesignMuramidaseProteinsThermolysinTrypsinMuramidaseProteinsSmall Molecule LibrariesThermolysinTrypsinacoustic droplet ejectionchemical biologydrug discoveryfragment screeningin situ X-ray data collectionprotein crystallizationsynchrotron radiation

Identifiers

PMID24816088
PMCPMC4014116

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Registered trials

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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.