The new Fragment-Screen project aims to develop innovative instrumentation, workflows and experimental and computational methodologies for fragment-based drug discovery (FBDD).

EU-OPENSCREEN leads Work Package 6 on "Fragment-to-lead optimisation supported by AI", with the support of four EU-OPENSCREEN chemistry partner sites: Faculdade de Farmácia da Universidade de Lisboa (Portugal), Technical University of Denmark (DTU), Consejo Superior de Investigaciones Científicas (CSIC), Madrid (Spain) and Latvian Institute of Organic Synthesis, Riga (Latvia).

Wolfgang Fecke, EU-OPENSCREEN Director General, said, “This project is an exciting continuation of the successful collaboration between Instruct-ERIC and EU-OPENSCREEN in the field of FBDD. By applying Artificial Intelligence methods, this project takes our collaboration to the next level.”

Tanja Miletic, Scientific Project Manager at EU-OPENSCREEN, added, “We will work on four SARS-CoV-2 protein targets, addressing an ongoing urgent medical need. The outcomes of Fragment-Screen will directly feed into other European projects, in which EU-OPENSCREEN participates, like ISIDORe and canSERV.”

Over the last years, fragment-based drug discovery is increasingly utilised both in pharmaceutical industry but also in academic settings to develop new chemical matter targeting protein targets. FBDD already has a proven track record of drug generation, with FDA approval given in several cases. Up to now, NMR and crystallography are used for screening of compound libraries typically containing 1000 compounds.

Coordinated by Instruct-ERIC, the EU-funded project Fragment-Screen will now take the next step. It will improve current bottlenecks in signal-to-noise (NMR), automation of data analysis (X-ray), and general applicability of cryo-EM for high-throughput. It will help make data analysis coherent over different methodological approaches. Mass spectrometry will be implemented for the first time to provide highly valuable cross-validation technology.

Harald Schwalbe, Instruct-ERIC Director, said, “I consider the Fragment-Screen project to transform fragment-based drug discovery. Within this, we could successfully bring together not only Structural Biologists and Medicinal Chemists, but also major European technology organisations, as well as companies in the rapidly growing field of Artificial Intelligence. At the end of the project, the process of drug development will be substantially improved.”

The research infrastructures central to the project are:

• Instruct-ERIC (Coordinator): Structural Biology
• EU-OPENSCREEN: Chemical Biology
• ELIXIR: Data Resources for Life Science
• ESRF: European Synchrotron
• Diamond Light Source
• European Molecular Biology Laboratory (EMBL)

Additionally, seven industry partners are involved, providing experience and will co-develop instrumentation with other partners to remove key bottlenecks that appear in the drug discovery process.

These industrial partners include:

• Bruker Biospin GMBH
• Signals
• Arinax
• Astex Therapeutics
• ALPX SAS
• FEI Electron Optics BV
• IBM Research GMBH