The HZB F2X‐Facility—An Efficient Crystallographic Fragment Screening Platform DOI Creative Commons
T. Barthel, L.S. Benz,

Yara Basler

и другие.

Applied Research, Год журнала: 2024, Номер unknown

Опубликована: Сен. 16, 2024

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 automation as well specialized workflows robust analysis tools. Consequently, large‐scale research facilities such synchrotrons have embraced method, developed platforms to perform CFS campaigns with help crystallography experts specific The BESSY II synchrotron, operated by Helmholtz–Zentrum Berlin (HZB), one these synchrotron that offer platform, named F2X‐facility. Here, F2X workflow described along relevant differences other existing platforms, ongoing developments aimed at supporting users facility. different campaign including requirements, beamline capabilities, software environment are detailed explained. A unique F2X‐GO kit featured, which allows possibility performing all sample preparation in their home laboratories. Furthermore, HZB computational been built support beyond hit identification stage. advantages F2X‐facility references provided successfully conduct CFS.

Язык: Английский

Different applications and differentiated libraries for crystallographic fragment screening DOI Creative Commons
Jessica E. Watt, Mathew P. Martin, Jane Endicott

и другие.

Current Opinion in Structural Biology, Год журнала: 2025, Номер 90, С. 102982 - 102982

Опубликована: Янв. 18, 2025

Macromolecular X-ray crystallography allows detection and characterisation of the binding small, low-affinity chemical fragments. Here we review utility fragment screening for drug discovery, its potential use in discovery science, as well some distinct types fragments that have been compiled into libraries.

Язык: Английский

Процитировано

0
How to Find a Fragment: Methods for Screening and Validation in Fragment‐Based Drug Discovery DOI
Tim Kirkman, Catharina dos Santos Silva, Manuela Tosin

и другие.

ChemMedChem, Год журнала: 2024, Номер 19(24)

Опубликована: Авг. 29, 2024

Abstract Fragment‐based drug discovery (FBDD) is a crucial strategy for developing new drugs that have been applied to diverse targets, from neglected infectious diseases cancer. With at least seven already launched the market, this approach has gained interest in both academics and industry last 20 years. FBDD relies on screening small libraries with about 1000–2000 compounds of low molecular weight (about 300 Da) using several biophysical methods. Because reduced size compounds, chemical space diversity can be better explored than large used high throughput screenings. This review summarises most common techniques fragment orthogonal validation. We also explore advantages drawbacks different examples applications strategies.

Язык: Английский

Процитировано

3
Accelerating Drug Discovery With High‐Throughput Crystallographic Fragment Screening and Structural Enablement DOI Creative Commons
D. Fearon, A.J. Powell, A. Douangamath

и другие.

Applied Research, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 24, 2024

ABSTRACT Fragment‐based drug discovery is a well‐established method for the identification of chemical starting points development into clinical candidates. Historically, crystallographic fragment screening was perceived to be low‐throughput and time consuming. However, thanks advances in synchrotron capabilities introduction dedicated facilities, such as XChem platform at Diamond Light Source, there have been substantial improvements throughput integration between sample preparation, data collection hit identification. Herein we share our experiences establishing facility, learnings from operating user programme ten years perspective on applying structural enablement rapidly progress initial hits lead‐like molecules.

Язык: Английский

Процитировано

3
HEIDI: an experiment-management platform enabling high-throughput fragment and compound screening DOI Creative Commons
A. Metz, Dennis P. Stegmann, Ezequiel Panepucci

и другие.

Acta Crystallographica Section D Structural Biology, Год журнала: 2024, Номер 80(5), С. 328 - 335

Опубликована: Апрель 12, 2024

The Swiss Light Source facilitates fragment-based drug-discovery campaigns for academic and industrial users through the Fast Fragment Compound Screening (FFCS) software suite. This framework is further enriched by option to utilize Smart Digital User (SDU) automated data collection across PXI, PXII PXIII beamlines. In this work, newly developed HEIDI webpage (https://heidi.psi.ch) introduced: a platform crafted using state-of-the-art architecture web technologies sample management of rotational experiments. features data-review tab enhanced result visualization provides programmatic access representational state transfer application programming interface (REST API). migration local FFCS MongoDB instance cloud highlighted detailed. transition ensures secure, encrypted consistently accessible robust reliable REST API tailored Collectively, these advancements not only significantly elevate user experience, but also pave way future expansions improvements in capabilities system.

Язык: Английский

Процитировано

2
Cryo2RT: a high-throughput method for room-temperature macromolecular crystallography from cryo-cooled crystals DOI Creative Commons
Chia‐Ying Huang, Sylvain Aumonier, Vincent Oliéric

и другие.

Acta Crystallographica Section D Structural Biology, Год журнала: 2024, Номер 80(8), С. 620 - 628

Опубликована: Июль 25, 2024

Advances in structural biology have relied heavily on synchrotron cryo-crystallography and cryogenic electron microscopy to elucidate biological processes for drug discovery. However, disparities between room-temperature (RT) crystal structures pose challenges. Here, Cryo2RT, a high-throughput RT data-collection method from cryo-cooled crystals that leverages the workflow, is introduced. Tested endothiapepsin with four soaked fragments, thaumatin SARS-CoV-2 3CL pro , Cryo2RT reveals unique ligand-binding poses, offers comparable throughput eases exploration of dynamics at various temperatures.

Язык: Английский

Процитировано

0
The HZB F2X‐Facility—An Efficient Crystallographic Fragment Screening Platform DOI Creative Commons
T. Barthel, L.S. Benz,

Yara Basler

и другие.

Applied Research, Год журнала: 2024, Номер unknown

Опубликована: Сен. 16, 2024

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 automation as well specialized workflows robust analysis tools. Consequently, large‐scale research facilities such synchrotrons have embraced method, developed platforms to perform CFS campaigns with help crystallography experts specific The BESSY II synchrotron, operated by Helmholtz–Zentrum Berlin (HZB), one these synchrotron that offer platform, named F2X‐facility. Here, F2X workflow described along relevant differences other existing platforms, ongoing developments aimed at supporting users facility. different campaign including requirements, beamline capabilities, software environment are detailed explained. A unique F2X‐GO kit featured, which allows possibility performing all sample preparation in their home laboratories. Furthermore, HZB computational been built support beyond hit identification stage. advantages F2X‐facility references provided successfully conduct CFS.

Язык: Английский

Процитировано

0