Contact information
frank.vondelft@cmd.ox.ac.uk
frank.von-delft@diamond.ac.uk
https://orcid.org/0000-0003-0378-0017
NDM Research Building
Frank von Delft
Professor of Structural Chemical Biology
My overall research project is to establish methods to ensure that X-ray structures can serve as a routine and predictive tool for generating novel chemistry for targeting proteins - as opposed to them being only occasionally and retrospectively useful descriptively, as is currently generally the case.
I am head of the Protein Crystallography SRF of the Centre for Medicines Discovery (CMD), which grew from the Oxford site of the Structural Genomics Consortium. I am also, jointly, Principal Beamline Scientist of beamline I04-1 at Diamond Light Source synchrotron (Harwell). After my PhD in protein crystallography with Tom Blundell in Cambridge, I have focused on methodology and high throughput techniques for crystallography, first in San Diego (academically at JCSG, and industrially at Syrrx, Inc), and since 2004 at the SGC, where my group helped solve over 650 crystal structures of human proteins.
As structural biologist, I am trying to help reshape how protein structure determination transforms rational drug design, by developing and making the new methodologies and tools available through platforms and products to ensure they are widely and routinely used by researchers world-wide. My long-term programme is to shrink by two orders of magnitude the time and cost required to develop small molecule inhibitors, by combining national facilities, artificial intelligence, robotics and cloud-based open access science, in order to make the bespoke design of inhibitors a consistently cheap, fast and widely-used approach in biology and medicine.
In late 2012 I also joined Diamond, to configure beamline I04-1 into a user facility for routine fragment screening by X-ray structures: this XChem facility has since supported large numbers of discovery projects from academia and industry. Accordingly, my research addresses the challenges both the upstream and downstream of the fragment screen: how to generate crystals that are suitable for such screening, and afterwards, how to proceed routinely from such a screen to compounds with biologically relevant affinity.
The research approach is two-pronged: developing the infrastructure (robotics, hardware, beamline) required to drive the throughput necessary for identifying the most appropriate samples at each step in the experimental process; and improving the methodology available at each step.
During the COVID-19 pandemic, I co-founded the COVID Moonshot, and antiviral drug discovery now forms part of my active research.
Recent publications
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Crystallographic fragment screening of the dengue virus polymerase reveals multiple binding sites for the development of non-nucleoside antiflavivirals
Saini M. et al, (2025)
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Crystallographic fragment screening and deep mutational scanning of Zika virus NS2B-NS3 protease enable development of resistance-resilient inhibitors
von Delft F. et al, (2025)
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Heterologous production, purification and crystallization of 24C-sterol methyltransferase fromCandida albicans
Mpontshane NS. et al, (2025)
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Dengue 2 NS2B-NS3 protease binding assay for compound screen using grating-coupled interferometry v1
Capkin E. et al, (2025)
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Binding-Site Purification of Actives (B-SPA) Enables Efficient Large-Scale Progression of Fragment Hits by Combining Multi-Step Array Synthesis With HT Crystallography.
Grosjean H. et al, (2025), Angewandte Chemie (International ed. in English)