Search Results

You searched for all publications:

with publication states 'Published (Approved)'

Search Again...

These results only include publications that have been reviewed and processed by Diamond Light Source. To also view papers that have not yet been processed click here.

You can use the folder icon under Actions to collate papers as required. You can then click on View Folder in the left-hand navigation to review and/or download your folder.

Exact matches
Related results

48 items found (0 items not approved), displaying 1 to 10.[First/Prev] 1, 2, 3, 4, 5 [Next/Last]

Instruments / Technical Area	Publication Details	Published
I24-Microfocus Macromolecular Crystallography Detectors	Experience with the Jungfrau-1M detector at Diamond Light Source John Matheson , Danny Axford , Anna Bergamaschi , Maria Carulla , Nicholas Devenish , Noemi Frisina , Viktoria Hinger , Vadym Kedych , Christopher Lane , Aldo Mozzanica , Eva Gimenez-Navarro , James O'Hea , Dominic Oram , Robin L. Owen , David Perl , Adam Prescott , Bernd Schmitt , Shane Scully , Adam Taylor , Gary Yendell , Graeme Winter Journal Of Synchrotron Radiation 33 DOI: 10.1107/S1600577526000342 Open Access Show Abstract ▼ Abstract: A Jungfrau-1M detector has undergone testing at Diamond Light Source. The Jungfrau series of detectors from PSI use integration and adaptive gain, to offer very high frame rate and dynamic range, suitable for high-flux and time-resolved measurements. They are becoming more widely used, to take advantage of increasing light source brightness. We report on our experiences in testing the performance of a Jungfrau-1M without illumination, with a laboratory X-ray tube and on a microfocus beamline. The Jungfrau-1M was found to be able to resolve single photons in the laboratory and on the beamline. It was confirmed that range switching from high to intermediate gain is associated with a discontinuity in the detector response. Two methods of dark frame subtraction were compared for their effect on minimizing this discontinuity. The Jungfrau-1M was found to be very effective for recording macromolecular crystallography diffraction patterns, with no apparent detriment from the discontinuity. The Diamond machine will be upgraded in 2028–9 and will operate at significantly higher flux than at present, necessitating increased use of integrating detectors, such as Jungfrau, in the future.	Mar 2026
I24-Microfocus Macromolecular Crystallography Detectors	Climbing mountains: building a data capture and correction system for JUNGFRAU 9M Graeme Winter , Nick E. Devenish , James O'Hea , Gary Yendell 75th Annual Meeting of the American Crystallographic Association DOI: 10.1063/4.0000827 Open Access Show Abstract ▼ Abstract: The JUNGFRAU detector is a charge integrating, high-frame-rate, imaging detector developed by the PSI detector group, originally to support the SwissFEL Aramis beamline. The detector includes adaptive gain switching to give single photon sensitivity whilst also allowing sufficient analogue dynamic range to record ∼10,000 12keV photons. The use of adaptive gains requires a multi-stage data correction procedure, factoring in the pedestal and gain value for each pixel for each gain mode: at 2kHz frame rate this makes for a non-trivial undertaking. At the SLS a data capture system for this has been developed, JUNGFRAUJOCH which uses a number of Xilinx FPGA boards to read the UDP data stream and perform the correction and the initial stage of data compression, before reading out to the CPU for compression. Whilst this is an effective solution, the technology choice of FPGA high level synthesis for programming has a very high barrier to entry. Some kind of hardware acceleration is however critical to ensure the correction and compression keep up with the data acquisition rate over the long term. At Diamond we are also acquiring a JUNGFRAU 9M detector, to use for rotation and serial crystallography on beamline I24. This brings us to the challenge: adopt JUNGFRAUJOCH or develop an alternative system, since the wider view of high throughput computing has changed over the last few years. Here we present an alternative system build around the NVIDIA Grace Hopper Superchip (GH200) which includes a 72 ARM NEOVERSE v2 CPU cores, an NVIDIA H100 GPU and high bandwidth memory (Figure 1). The capabilities of this system allow us to consider building a data capture, correction and initial analysis system to support the JUNGFRAU 9M detector at Diamond Light Source, using far more mainstream technologies (CUDA for the accelerator programming, SLS detector for the front-end data capture) and offering the opportunity to tailor the system to fit in with the use cases being developed at Diamond Light Source beamline I24. This development also takes the opportunity to explore alternative methods for representing the data, keeping the data from modules separated allowing parallelism in data capture and analysis.	Oct 2025
I19-Small Molecule Single Crystal Diffraction	Segmented milli-fluidic crystallisation of paracetamol with in situ single-crystal X-ray diffraction Karen Robertson , Mark R. Warren , Lois E. Wayment , Pollyanna Payne , C. Daniel Scott , Chick C. Wilson , Lucy K. Saunders , Graeme Winter , Benjamin Williams , Lauren E. Hatcher , David R. Allan Chemical Science DOI: 10.1039/D4SC08565E Diamond Proposal Number(s): [22497, 21301] Open Access Show Abstract ▼ Abstract: Serial crystallography has revolutionalised our ability to analyse protein crystals; crystal structures can be uncovered by combining data from multiple crystals mitigating radiation damage through overexposure to the X-ray beam. With synchrotron sources becoming even brighter radiation damage is ever more pertinent for small molecule crystals as well. Combining serial crystallography with flow crystallisation, we pave the way to exploring high-throughput screening and kinetic studies, and application to small molecule crystals of up to mm-scale. Here we present the first known example of single crystal X-ray diffraction of small molecule crystals in a flow crystallisation environment. In situ single-crystal X-ray diffraction has been achieved on a series of growing singular crystals through use of segmented flow cooling crystallisation, holding crystals in the X-ray beam for 4.2 s whilst they freely rotate whilst flowing inside tubing. Upon triggering of a passing slug at the analysis point, the tubing is moved in the opposite direction to the flow, enabling the crystal to remain within the X-ray beam whilst maintaining the free rotation of the crystal due to fluid movement. Structure solution of paracetamol Form I has been achieved with 0.8 Å resolution using data combined from 13 crystals whilst unit cell information can be extracted from a single crystal.	Jun 2025
I24-Microfocus Macromolecular Crystallography VMXi-Versatile Macromolecular Crystallography in situ	Enhanced intensity-based clustering of isomorphous multi-crystal data sets in the presence of subtle variations Amy J. Thompson , James Beilsten-Edmands , Cicely Tam , Juan Sanchez-Weatherby , James Sandy , Halina Mikolajek , Danny Axford , Sofia Jaho , Michael A. Hough , Graeme Winter Acta Crystallographica Section D Structural Biology 81, 278 - 290 DOI: 10.1107/S2059798325004589 Open Access Show Abstract ▼ Abstract: Multi-crystal processing of X-ray diffraction data has become highly automated to keep pace with the current high-throughput capabilities afforded by beamlines. A significant challenge, however, is the automated clustering of such data based on subtle differences such as ligand binding or conformational shifts. Intensity-based hierarchical clustering has been shown to be a viable method of identifying such subtle structural differences, but the interpretation of the resulting dendrograms is difficult to automate. Using isomorphous crystals of bovine, porcine and human insulin, the existing clustering methods in the multi-crystal processing software xia2.multiplex were validated and their limits were tested. It was determined that weighting the pairwise correlation coefficient calculations with the intensity uncertainties was required for accurate calculation of the pairwise correlation coefficient matrix (correlation clustering) and dimension optimization was required when expressing this matrix as a set of coordinates representing data sets (cosine-angle clustering). Finally, the introduction of the OPTICS spatial density-based clustering algorithm into DIALS allowed the automatic output of species-pure clusters of bovine, porcine and human insulin data sets.	Jun 2025
	Accelerating drug discovery with high-throughput crystallographic fragment screening and structural enablement Daren Fearon , Ailsa Powell , Alice Douangamath , Alexandre Dias , Charles W. E. Tomlinson , Blake H. Balcomb , Jasmin C. Aschenbrenner , Anthony Aimon , Isabel A. Barker , Jose Brandao-Neto , Patrick Collins , Louise E. Dunnett , Michael Fairhead , Richard J. Gildea , Mathew Golding , Tyler Gorrie-Stone , Paul V. Hathaway , Lizbe Koekemoer , Tobias Krojer , Ryan Lithgo , Elizabeth M. Maclean , Peter G. Marples , Xiaomin Ni , Rachael Skyner , Romain Talon , Warren Thompson , Conor F. Wild , Max Winokan , Nathan D. Wright , Graeme Winter , Elizabeth J. Shotton , Frank Von Delft Applied Research DOI: 10.1002/appl.202400192 Open Access Show Abstract ▼ 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.	Nov 2024
I24-Microfocus Macromolecular Crystallography	Processing serial synchrotron crystallography diffraction data with DIALS James Beilsten-Edmands , James M. Parkhurst , Graeme Winter , Gwyndaf Evans DOI: 10.1016/bs.mie.2024.10.004 Show Abstract ▼ Abstract: This chapter describes additions to the DIALS software package for processing serial still-shot crystallographic data, and the implementation of a pipeline, xia2.ssx, for processing and merging serial crystallography data using DIALS programs. To integrate partial still-shot diffraction data, a 3D gaussian profile model was developed that can describe anisotropic spot shapes. This model is optimised by maximum likelihood methods using the pixel-intensity distributions of strong diffraction spots, enabling simultaneous refinement of the profile model and Ewald-sphere offsets. We demonstrate the processing of an example SSX dataset where the improved partiality estimates lead to better model statistics compared with post-refined isotropic models. We also demonstrate some of the workflows available for merging SSX data, including processing time/dose resolved data series, where data can be separated at the point of merging after scaling and discuss the program outputs used to investigate the data throughout the pipeline.	Nov 2024
I23-Long wavelength MX	Ray-tracing analytical absorption correction for X-ray crystallography based on tomographic reconstructions Yishun Lu , Ramona Duman , James Beilsten-Edmands , Graeme Winter , Mark Basham , Gwyndaf Evans , Jos J. A. G. Kamps , Allen M. Orville , Hok-Sau Kwong , Konstantinos Beis , Wesley Armour , Armin Wagner Journal Of Applied Crystallography 57 DOI: 10.1107/S1600576724002243 Open Access Show Abstract ▼ Abstract: rocessing of single-crystal X-ray diffraction data from area detectors can be separated into two steps. First, raw intensities are obtained by integration of the diffraction images, and then data correction and reduction are performed to determine structure-factor amplitudes and their uncertainties. The second step considers the diffraction geometry, sample illumination, decay, absorption and other effects. While absorption is only a minor effect in standard macromolecular crystallography (MX), it can become the largest source of uncertainty for experiments performed at long wavelengths. Current software packages for MX typically employ empirical models to correct for the effects of absorption, with the corrections determined through the procedure of minimizing the differences in intensities between symmetry-equivalent reflections; these models are well suited to capturing smoothly varying experimental effects. However, for very long wavelengths, empirical methods become an unreliable approach to model strong absorption effects with high fidelity. This problem is particularly acute when data multiplicity is low. This paper presents an analytical absorption correction strategy (implemented in new software AnACor) based on a volumetric model of the sample derived from X-ray tomography. Individual path lengths through the different sample materials for all reflections are determined by a ray-tracing method. Several approaches for absorption corrections (spherical harmonics correction, analytical absorption correction and a combination of the two) are compared for two samples, the membrane protein OmpK36 GD, measured at a wavelength of λ = 3.54 Å, and chlorite dismutase, measured at λ = 4.13 Å. Data set statistics, the peak heights in the anomalous difference Fourier maps and the success of experimental phasing are used to compare the results from the different absorption correction approaches. The strategies using the new analytical absorption correction are shown to be superior to the standard spherical harmonics corrections. While the improvements are modest in the 3.54 Å data, the analytical absorption correction outperforms spherical harmonics in the longer-wavelength data (λ = 4.13 Å), which is also reflected in the reduced amount of data being required for successful experimental phasing.	Jun 2024
I03-Macromolecular Crystallography I23-Long wavelength MX	Experimental phasing opportunities for macromolecular crystallography at very long wavelengths Kamel El Omari , Ramona Duman , Vitaliy Mykhaylyk , Christian M. Orr , Merlyn Latimer-Smith , Graeme Winter , Vinay Grama , Feng Qu , Kiran Bountra , Hok Sau Kwong , Maria Romano , Rosana Reis , Lutz Vogeley , Luca Vecchia , C. David Owen , Sina Wittmann , Max Renner , Miki Senda , Naohiro Matsugaki , Yoshiaki Kawano , Thomas A. Bowden , Isabel Moraes , Jonathan M. Grimes , Erika J. Mancini , Martin A. Walsh , Cristiane R. Guzzo , Raymond J. Owens , E. Yvonne Jones , David G. Brown , Dave I. Stuart , Konstantinos Beis , Armin Wagner Communications Chemistry 6 DOI: 10.1038/s42004-023-01014-0 Open Access Show Abstract ▼ Abstract: Despite recent advances in cryo-electron microscopy and artificial intelligence-based model predictions, a significant fraction of structure determinations by macromolecular crystallography still requires experimental phasing, usually by means of single-wavelength anomalous diffraction (SAD) techniques. Most synchrotron beamlines provide highly brilliant beams of X-rays of between 0.7 and 2 Å wavelength. Use of longer wavelengths to access the absorption edges of biologically important lighter atoms such as calcium, potassium, chlorine, sulfur and phosphorus for native-SAD phasing is attractive but technically highly challenging. The long-wavelength beamline I23 at Diamond Light Source overcomes these limitations and extends the accessible wavelength range to λ = 5.9 Å. Here we report 22 macromolecular structures solved in this extended wavelength range, using anomalous scattering from a range of elements which demonstrate the routine feasibility of lighter atom phasing. We suggest that, in light of its advantages, long-wavelength crystallography is a compelling option for experimental phasing.	Oct 2023
Krios I-Titan Krios I at Diamond	A standard data format for 3DED/MicroED David G. Waterman , Noemi Frisina , C. David Owen , Graeme Winter , Pedro Nunes Structure 5 DOI: 10.1016/j.str.2023.07.004 Open Access Show Abstract ▼ Abstract: Electron diffraction from three dimensional crystals, as a technique for solving molecular structures, is rapidly increasing in popularity. The development of methodology and software has borrowed, to great effect, from macromolecular X-ray crystallography. However, standardization lags behind the development of the technique, and practitioners are forced to work with inadequate data formats that are unable to capture a full description of their experiments. This creates obstacles that are increasingly difficult to overcome as experiments become ever faster and the need for data autoprocessing becomes more pressing. We present a data format standard based on best practice from macromolecular crystallography and demonstrate how the adoption of this standard enabled autoprocessing of datasets collected with a high-throughput detector system.	Aug 2023
	The CCP 4 suite: integrative software for macromolecular crystallography Jon Agirre , Mihaela Atanasova , Haroldas Bagdonas , Charles B. Ballard , Arnaud Basle , James Beilsten-Edmands , Rafael J. Borges , David G. Brown , J. Javier Burgos-Marmol , John M. Berrisford , Paul S. Bond , Iracema Caballero , Lucrezia Catapano , Grzegorz Chojnowski , Atlanta G. Cook , Kevin D. Cowtan , Tristan I. Croll , Judit É. Debreczeni , Nicholas E. Devenish , Eleanor J. Dodson , Tarik R. Drevon , Paul Emsley , Gwyndaf Evans , Phil R. Evans , Maria Fando , James Foadi , Luis Fuentes-Montero , Elspeth F. Garman , Markus Gerstel , Richard J. Gildea , Kaushik Hatti , Maarten L. Hekkelman , Philipp Heuser , Soon Wen Hoh , Michael A. Hough , Huw T. Jenkins , Elisabet Jiménez , Robbie P. Joosten , Ronan M. Keegan , Nicholas Keep , Eugene B. Krissinel , Petr Kolenko , Oleg Kovalevskiy , Victor S. Lamzin , David M. Lawson , Andrey Lebedev , Andrew G. W. Leslie , Bernhard Lohkamp , Fei Long , Martin Maly , Airlie Mccoy , Stuart J. Mcnicholas , Ana Medina , Claudia Millán , James W. Murray , Garib N. Murshudov , Robert A. Nicholls , Martin E. M. Noble , Robert Oeffner , Navraj S. Pannu , James M. Parkhurst , Nicholas Pearce , Joana Pereira , Anastassis Perrakis , Harold R. Powell , Randy J. Read , Daniel J. Rigden , William Rochira , Massimo Sammito , Filomeno Sanchez Rodriguez , George M. Sheldrick , Kathryn L. Shelley , Felix Simkovic , Adam J. Simpkin , Pavol Skubak , Egor Sobolev , Roberto A. Steiner , Kyle Stevenson , Ivo Tews , Jens M. H. Thomas , Andrea Thorn , Josep Triviño Valls , Ville Uski , Isabel Uson , Alexei Vagin , Sameer Velankar , Melanie Vollmar , Helen Walden , David Waterman , Keith S. Wilson , Martyn Winn , Graeme Winter , Marcin Wojdyr , Keitaro Yamashita Acta Crystallographica Section D Structural Biology 79, 449 - 461 DOI: 10.1107/S2059798323003595 Open Access Show Abstract ▼ Abstract: The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with a mission to develop, test, distribute and promote software for macromolecular crystallography. The CCP4 suite is a multiplatform collection of programs brought together by familiar execution routines, a set of common libraries and graphical interfaces. The CCP4 suite has experienced several considerable changes since its last reference article, involving new infrastructure, original programs and graphical interfaces. This article, which is intended as a general literature citation for the use of the CCP4 software suite in structure determination, will guide the reader through such transformations, offering a general overview of the new features and outlining future developments. As such, it aims to highlight the individual programs that comprise the suite and to provide the latest references to them for perusal by crystallographers around the world.	Jun 2023

Publications Database

Search Results

You searched for all publications:

Search Again...

Subject Areas (check all that apply) select all

Instruments used to collect data (check all that apply) select all

Collaborations involved (check all that apply) select all

Diamond Offline Facilities used

Relevant Technical Areas (check all that apply) select all

Menu for Anonymous User