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The HZB F2X-facility -- an efficient crystallographic fragment screening platform
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  • Tatjana Barthel,
  • Laila Benz,
  • Yara Basler,
  • Thomas Crosskey,
  • Alexander Dillmann,
  • Ronald Förster,
  • Paula Fröling,
  • Camilla Genter Dieguez,
  • Christine Gless,
  • Thomas Hauß,
  • Michael Hellmig,
  • Lea Jänisch,
  • David James,
  • Frank Lennartz,
  • Jelena Mijatovic,
  • Melanie Oelker,
  • James William Scanlan,
  • Gert Weber,
  • Jan Wollenhaupt,
  • Uwe Mueller,
  • Holger Dobbek,
  • Markus C. Wahl,
  • Manfred S. Weiss
Tatjana Barthel
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Laila Benz
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Yara Basler
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Thomas Crosskey
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Alexander Dillmann
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Ronald Förster
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Paula Fröling
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Camilla Genter Dieguez
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Christine Gless
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Thomas Hauß
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Michael Hellmig
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Lea Jänisch
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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David James
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Frank Lennartz
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Jelena Mijatovic
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Melanie Oelker
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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James William Scanlan
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Gert Weber
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Jan Wollenhaupt
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Uwe Mueller
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Holger Dobbek
Humboldt-Universitat zu Berlin Institut fur Biologie
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Markus C. Wahl
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH
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Manfred S. Weiss
Helmholtz-Zentrum Berlin fur Materialien und Energie GmbH

Corresponding Author:[email protected]

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Abstract

Crystallographic fragment screening (CFS) has recently matured into an important method for the early stages of drug discovery projects. It is based on high-throughput structure determination and thus requires a high degree of automation as well as specialized workflows and robust analysis tools. Consequently, large-scale research facilities such as synchrotrons have embraced the method, and developed platforms to perform CFS campaigns with the help of crystallography experts and specific tools. The BESSY II synchrotron, operated by the Helmholtz-Zentrum Berlin (HZB), is one of these synchrotron facilities that offer a CFS platform, named the F2X-facility. Here, the specialized F2X workflow is described along with the relevant differences to other existing CFS platforms, and the ongoing developments aimed at supporting users of the facility. The different stages of a CFS campaign including requirements, beamline capabilities, and the software environment are detailed and explained. A unique F2X-GO kit is featured, which allows users the possibility of performing all sample preparation in their home laboratories. Furthermore, at the HZB a computational workflow has been built to support users beyond the hit identification stage. The advantages of the F2X-facility at HZB are described and references are provided to successfully conduct CFS.
08 Jun 2024Submitted to Applied Research
14 Jun 2024Submission Checks Completed
14 Jun 2024Assigned to Editor
06 Jul 2024Review(s) Completed, Editorial Evaluation Pending
17 Jul 2024Editorial Decision: Revise Minor
06 Aug 20241st Revision Received
06 Aug 2024Submission Checks Completed
06 Aug 2024Assigned to Editor
08 Aug 2024Reviewer(s) Assigned
13 Aug 2024Review(s) Completed, Editorial Evaluation Pending
19 Aug 2024Editorial Decision: Accept