From fragments to high affinity binders interfacing integrated structural biology, medicinal chemistry and artificial intelligence

Project Information

Fragment-Screen

Grant agreement ID: 101094131

DOI

10.3030/101094131

EC signature date 13 December 2022

Start date 1 February 2023

End date 31 January 2026

Funded under

• Research infrastructures

Total cost

€ 8 265 079,64

EU contribution

€ 8 265 079,64

Coordinated by

INSTRUCT-ERIC
United Kingdom

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Deliverables

Documents, reports (10)

Proof of concept for in situ room temperature FBDD at DLS

Report on in situ room temperature fragment based drug discovery at DLS

Definition and pilot implementation of data/metadata standards for FBDD-NMR

First analysis of the metafa for FBDD-NMR to be used in the project, together with their initial data management software

Map of training needs and competencies of the consortium

Report on training needs of the consortium partners, the skills of consortium partners and a gap analysis

ARIA enhancements for exploitation of new technologies

Report on changes to ARIA access management software towards better use of the new technologies

Native MS validation screens

Completion of first detailed validation screens from native MS

Interoperability of Fragalysis with existing workflows

Report on interoperability of workflows with Fragalysis

Make AI tools developed under task 6.1 available to the scientific community

AI tools and documentations developed will be made available to the community through open-source platform at https://github.com/IBM/AIBinder.

Detailed methods and protocols in place for medium throughput of fragment binding and binding location by MRMS native MS and top-down

Protocol for fragment binding, including sample preparation and instrumental parameters

Website and social media setup

Launch project website and social media channels

Communication Plan

Communication plan with proposed outreach activities within the Fragment-Screen project

Data Management Plan (1)

Project handbook and Data Management Plan

Publish a handbook documenting the project management processes, branding, and general project information for use by the consortium members. The handbook will include the project’s data management plan, specifying which type of data will be dealt with, and how they will meet FAIR principles to allow for their re-use for research.

Demonstrators, pilots, prototypes (1)

Pilot open, FAIR repository with FBDD datasets made available

First implementation of FBDD repository, coordinated by EBI

Publications

Book chapters (1)

Language Models in Molecular Discovery

Author(s): Nikita Janakarajan, Tim Erdmann, Sarath Swaminathan, Teodoro Laino, Jannis Born
Published in: Drug Development Supported by Informatics, 2024
Publisher: Springer Nature Singapore
DOI: 10.1007/978-981-97-4828-0_7

Peer reviewed articles (12)

Regression Transformer enables concurrent sequence regression and generation for molecular language modelling

Author(s): Jannis Born, Matteo Manica
Published in: Nature Machine Intelligence, 2022, ISSN 2522-5839
Publisher: Nature Machine Intelligence
DOI: 10.48550/arXiv.2202.01338

Design, quality and validation of the EU-OPENSCREEN fragment library poised to a high-throughput screening collection

Author(s): Jalencas, Xavier and Berg, Hannes and Espeland, Ludvik Olai and Sreeramulu, Sridhar and Kinnen, Franziska and Richter, Christian and Georgiou, Charis and Yadrykhinsky, Vladyslav and Specker, Edgar and Jaudzems, Kristaps and Miletić, Tanja and Harmel, Robe
Published in: RSC Medicinal Chemistry, 2024, ISSN 2632-8682
Publisher: RSC Medicinal Chemistry
DOI: 10.1039/D3MD00724C

The rise of automated curiosity-driven discoveries in chemistry

Author(s): Latimah Bustillo, Teodoro Laino, and Tiago Rodrigues
Published in: Chemical Science, 2023, ISSN 2041-6520
Publisher: Royal Society of Chemistry
DOI: 10.1039/D3SC03367H

Controlling the incorporation of fluorinated amino acids in human cells and its structural impact

Author(s): Azzurra Costantino, Lan B. T. Pham, Letizia Barbieri, Vito Calderone, Gili Ben-Nissan, Michal Sharon, Lucia Banci, Enrico Luchinat
Published in: Protein Science, 2024, ISSN 1572-3887
Publisher: Springer Verlag
DOI: 10.1002/PRO.4910

Biomacromolecules

Author(s): Fallarini S.; Cerofolini L.; Salobehaj M.; Rizzo D.; Gheorghita G. R.; Licciardi G.; Capialbi D. E.; Zullo V.; Sodini A.; Nativi C.; Fragai M.
Published in: Biomacromolecules, 2023, ISSN 1525-7797
Publisher: American Chemical Society
DOI: 10.1021/acs.biomac.3c00893

Combining Solid‐State NMR with Structural and Biophysical Techniques to Design Challenging Protein‐Drug Conjugates

Author(s): Linda Cerofolini, Kristian Vasa, Elisa Bianconi, Maria Salobehaj, Giulia Cappelli, Alice Bonciani, Giulia Licciardi, Anna Pérez‐Ràfols, Luis Padilla‐Cortés, Sabrina Antonacci, Domenico Rizzo, Enrico Ravera, Caterina Viglianisi, Vito Calderone, Giacomo Parigi, Claudio Luchinat, Antonio Macchiarulo, Stefano Menichetti, Marco Fragai
Published in: Angewandte Chemie International Edition, Issue 62, 2023, ISSN 1433-7851
Publisher: Wiley
DOI: 10.1002/ANIE.202303202

Machine Learning-Enhanced Quantum Chemistry-Assisted Refinement of the Active Site Structure of Metalloproteins

Author(s): Lucia Gigli, José Malanho Silva, Linda Cerofolini, Anjos L. Macedo, Carlos F. G. C. Geraldes, Elizaveta A. Suturina, Vito Calderone, Marco Fragai, Giacomo Parigi, Enrico Ravera, Claudio Luchinat
Published in: Inorganic Chemistry, Issue 63, 2024, ISSN 0020-1669
Publisher: American Chemical Society (ACS)
DOI: 10.1021/ACS.INORGCHEM.4C01274

EasyGrid: A versatile platform for automated cryo-EM sample preparation and quality control

Author(s): Olivier Gemin, Victor Armijo, Michael Hons, Caroline Bissardon, Romain Linares, View ORCID ProfileMatthew W. Bowler, Georg Wolff, View ORCID ProfileKirill Kovalev, Anastasiia Babenko, Veijo T. Salo, Sarah Schneider, Christopher Rossi, Léa Lecomte, Thiba
Published in: bioRXiv, 2024, ISSN 2692-8205
Publisher: bioRXiv
DOI: 10.1101/2024.01.18.576170

Targeting the Main Protease (Mpro, nsp5) by Growth of Fragment Scaffolds Exploiting Structure-Based Methodologies

Author(s): Nadide Altincekic, Nathalie Jores, Frank Löhr, Christian Richter, Claus Ehrhardt, Marcel J. J. Blommers, Hannes Berg, Sare Öztürk, Santosh L. Gande, Verena Linhard, Julien Orts, Marie Jose Abi Saad, Matthias Bütikofer, Janina Kaderli, B. Göran Karlsson, U
Published in: ACS Chemical Biology, 2024, ISSN 1872-3136
Publisher: Bentham Science Publishers
DOI: 10.1021/ACSCHEMBIO.3C00720

eLife

Author(s): Isabelle Petit-Härtlein; Annelise Vermot; Michel Thépaut; Anne Sophie Humm; Florine Dupeux; Jérôme Dupuy; Vincent Chaptal; José A. Marquez; Susan M.E. Smith; Franck Fieschi
Published in: eLife, 2023, ISSN 2050-084X
Publisher: eLife Sciences Publications
DOI: 10.7554/ELIFE.93759

The future of integrated structural biology

Author(s): Harald Schwalbe, Pauline Audergon, Natalie Haley, Claudia Alen Amaro, Jon Agirre, Marc Baldus, Lucia Banci, Wolfgang Baumeister, Martin Blackledge, Jose Maria Carazo, Kristina Djinovic Carugo, Patrick Celie, Isabella Felli, Darren J. Hart, Thomas Hauß, Lari Lehtiö, Kresten Lindorff-Larsen, José Márquez, André Matagne, Roberta Pierattelli, Antonio Rosato, Frank Sobott, Sridhar Sreeramulu, Jan Steyaert, Joel L. Sussman, Lukas Trantirek, Manfred S. Weiss, Matthias Wilmanns
Published in: Structure, Issue 32, 2025, ISSN 0969-2126
Publisher: Cell Press
DOI: 10.1016/J.STR.2024.08.014

NMR 1H,19F-based screening of the four stem-looped structure 5_SL1–SL4 located in the 5′-untranslated region of SARS-CoV 2 RNA

Author(s): Daniel Hymon, Jason Martins, Christian Richter, Sridhar Sreeramulu, Anna Wacker, Jan Ferner, Neeraj N. Patwardhan, Amanda E. Hargrove, and Harald Schwalbe
Published in: RSC Medicinal Chemistry, 2024, ISSN 2632-8682
Publisher: RSC Medicinal Chemistry
DOI: 10.1039/D3MD00322A