Accelerating Drug Discovery With High‐Throughput Crystallographic Fragment Screening and Structural Enablement
ABSTRACT Fragment‐based drug discovery is a well‐established method for the identification of chemical starting points for development into clinical candidates. Historically, crystallographic fragment screening was perceived to be low‐throughput and time consuming. However, thanks to advances in synchrotron capabilities and the introduction of dedicated facilities, such as the XChem platform at Diamond Light Source, there have been substantial improvements in throughput and integration between sample preparation, data collection and hit identification. Herein we share our experiences of establishing a crystallographic fragment screening facility, our learnings from operating a user programme for ten years and our perspective on applying structural enablement to rapidly progress initial fragment hits to lead‐like molecules.
Authors
- Alexandre Dias (ORCID: https://orcid.org/0000-0003-3609-7003)
- Mathew Golding (ORCID: https://orcid.org/0009-0004-7472-8333)
- Charles W.E. Tomlinson (ORCID: https://orcid.org/0000-0002-1845-6028)
- Conor Wild (ORCID: https://orcid.org/0000-0003-0654-8141)
- T. Krojer (ORCID: https://orcid.org/0000-0003-0661-0814)
- Nathan D. Wright (ORCID: https://orcid.org/0000-0001-5035-8180)
- M. Fairhead (ORCID: https://orcid.org/0000-0001-5361-3933)
- Blake Balcomb (ORCID: https://orcid.org/0000-0001-7599-8467)
- T.J. Gorrie-Stone (ORCID: https://orcid.org/0000-0002-1817-1495)
- Elizabeth J. Shotton (ORCID: https://orcid.org/0000-0002-3330-0953)
- Warren Thompson (ORCID: https://orcid.org/0000-0003-1474-7810)
- Louise Dunnett (ORCID: https://orcid.org/0000-0001-6710-6959)
- R. Skyner (ORCID: https://orcid.org/0000-0003-3614-6661)
- A.J. Powell (ORCID: https://orcid.org/0000-0002-0462-2240)
- A. Douangamath (ORCID: https://orcid.org/0000-0002-9196-8644)
- A. Aimon (ORCID: https://orcid.org/0000-0002-9135-129X)
- Xiaomin Ni (ORCID: https://orcid.org/0000-0002-7769-8297)
- P.M. Collins (ORCID: https://orcid.org/0000-0002-6265-9922)
- J. Brandão-Neto (ORCID: https://orcid.org/0000-0001-6015-320X)
- Elizabeth MacLean (ORCID: https://orcid.org/0000-0003-1680-4292)
- Isabel A. Barker (ORCID: https://orcid.org/0009-0000-1207-032X)
- L. Koekemoer (ORCID: https://orcid.org/0000-0001-9226-9127)
- F. von Delft (ORCID: https://orcid.org/0000-0003-0378-0017)
- Ryan Lithgo (ORCID: https://orcid.org/0000-0002-4706-9916)
- Richard J. Gildea (ORCID: https://orcid.org/0000-0001-5038-6958)
- J.C. Aschenbrenner (ORCID: https://orcid.org/0000-0002-4318-0481)
- R. Talon (ORCID: https://orcid.org/0000-0003-1123-7241)
- Graeme Winter (ORCID: https://orcid.org/0000-0003-3165-0420)
- Paul Hathaway (ORCID: https://orcid.org/0000-0003-1432-4543)
- D. Fearon (ORCID: https://orcid.org/0000-0003-3529-7863)
- Max Winokan (ORCID: https://orcid.org/0000-0002-1318-4422)
- Peter Marples (ORCID: https://orcid.org/0000-0002-8787-7969)
Institutions
- University of Johannesburg (ZA)
- Diamond Light Source (GB)
- University of Oxford (GB)
- Research Complex at Harwell (GB)
Publication Details
- Journal
- Applied Research
- Published
- 2024-11-24
- DOI
- https://doi.org/10.1002/appl.202400192
- Citations
- 28
- Primary Topic
- Computational Drug Discovery Methods
- Type
- article
- Field-Weighted Citation Impact
- 10.12
Funders
- Diamond Light Source
- Moonshot Research and Development Program