Design, Quality and Validation of the EU-OPENSCREEN Fragment Library Poised to a High-Throughput Screening Collection

The EU-OPENSCREEN (EU-OS) European Research Infrastructure Consortium (ERIC) is a multinational, not-for-profit initiative that integrates high-capacity screening platforms and chemistry groups across Europe to facilitate research in chemical biology and early drug discovery. EU-OS now also provides a fragment screening library (EFSL). In this paper, we describe the computational design, quality control and use case screenings of the EFSL. Using EFSL, eight fragment screening campaigns using different structural and biophysical methods have successfully identified fragment hits in the last two years (three of them in the Brenk lab). As one of the highlighted projects for antibiotics, the screening by Bio-Layer Interferometry (BLI) of the EFSL, the identification of a 35 µM fragment hit targeting the beta-ketoacyl-ACP synthase 2 (FabF), its binding confirmation to the protein by X-ray crystallography is also described. This work was also carried out at UiB making use of instrumentation provided by BiSS. Collectively, this work highlights the power of EFSL for rapid hit identifaction and follow-up.

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