scholarly journals I04-1, a future 'fragment screening' beamline facility at Diamond Light Source

2014 ◽  
Vol 70 (a1) ◽  
pp. C790-C790
Author(s):  
Alice Douangamath ◽  
Jose Brandao-Neto ◽  
Mark Williams ◽  
Richard Fearn ◽  
Tobias Krojer ◽  
...  
Keyword(s):  
Light Source ◽  
Macromolecular Crystallography ◽  
New Developments ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fragment Screening ◽  
The Third ◽  
Synchrotron Light ◽  
Set Up ◽  
The Uk

I04-1 is one of the six macromolecular crystallography (MX) beamlines at Diamond Light Source (DLS), the third generation synchrotron light source in the UK. It was built and delivered in 2010 as a stable and reliable fixed-wavelength MX station. It is currently preparing to release its user programme for exploiting fragment screening using X-ray crystallography in structural medicinal chemistry projects. For this purpose, the beamline has been going through several upgrades in order to achieve unattended high-throughput ligand crystallography. The new developments are aiming at improving the flux, stability and reliability of the beamline and its auto-alignment. In parallel, a peripheral laboratory is being set up to provide a facility for medium throughput compound soaking. Jointly with the Structural Genomics Consortium (SGC), a semi-automatic crystal soaking and harvesting scheme, which will provide hundreds of MX samples per day, is being tested at DLS. The beamline can currently process 400 crystals per day. However, the recent upgrades and automation should further improve that throughput. In this presentation, we will summarise the current specifications of the beamline and its new features, the development of a peripheral laboratory for compounds soaking and underline the remaining work.

scholarly journals Crystallography and the IYCr2014 in Uruguay and Latin America

2014 ◽  
Vol 70 (a1) ◽  
pp. C1288-C1288
Author(s):  
Leopoldo Suescun
Keyword(s):  
Latin America ◽  
Latin American ◽  
The Political ◽  
X Ray ◽  
X Ray Crystallography ◽  
Synchrotron Light ◽  
The Uk ◽  
People Group ◽  
Research Equipment

X-ray Crystallography has been present in Uruguay since the 50's. A project funded by UNESCO brought Prof. S. Furberg to Montevideo and introduced equipment in a laboratory of Universidad de la República, Facultad de Ingeniería where Prof. Stephenson Caticha Ellis worked.[1] During the period 1968-1995 the political and economic situation of the country reduced research in general and crystallography in particular, re-emerging in the late 90's with the acquisition of an automatic single-crystal diffractometer by Facultad de Química. After the opening of the Brazilian Synchrotron Light Laboratory in 1997 several projects in crystallography have also developed with the successful realization of half a dozen postgraduate projects. Currently there are chemical, biological and physical crystallography labs in the country, with a reduced but sufficient pool of research equipment. The main institutions where Crystallography is developed are Universidad de la República (3 groups) and the Institut Pasteur de Montevideo. There has been an explosive growth of crystallography in the country in recent years. From the 4-people group found at F. de Química in 2000 to over 50 people of the Red Uruguaya de Cristalografía recently founded.[2] This development wouldn't have happened without the strong influence of Latin American crystallographers, mainly but not only from Argentina and Brazil, and also collaboration from extra-regional colleagues from USA, the UK, France and Switzerland. Very recently additional impulse has come from Latin America with the formation of the Latin American Cryst. Assoc. LACA[3]. Uruguayan crystallographers are currently involved in dissemination and academic projects for IYCr2014 such as an open-sky photo-gallery in Montevideo, a national crystal growth competition, a protein crystallography school and two UNESCO/IUCr OpenLab Type 1 sponsored by Bruker. A description of on-going projects in Uruguay and the region will be outlined in the presentation

Upgrade of BL-5C as a highly automated macromolecular crystallography beamline at Pohang Light Source II

2021 ◽  
Vol 28 (2) ◽  
pp. 602-608
Author(s):  
Jae-Hee Jeong ◽  
Cheolsoo Eo ◽  
Hyo-Yun Kim ◽  
Jin-Hong Kim ◽  
Chae-Soon Lee ◽  
...  
Keyword(s):  
Light Source ◽  
Photon Counting ◽  
High Capacity ◽  
Spot Size ◽  
Data Sets ◽  
Macromolecular Crystallography ◽  
X Ray ◽  
Photon Counting Detector ◽  
Fragment Screening ◽  
Pohang Light Source

BL-5C is an in-vacuum undulator beamline dedicated to macromolecular crystallography (MX) at the 3 GeV Pohang Light Source II in Korea. The beamline delivers X-ray beams with a focal spot size of 200 µm × 40 µm (FWHM, H × V) over the energy range 6.5–16.5 keV. The measured flux is 7 × 1011 photons s−1 at 12.659 keV through an aperture size of 50 µm. The experimental station is newly equipped with the photon-counting detector EIGER 9M, the multi-axis micro-diffractometer MD2, and a robotic sample changer with a high-capacity dewar. These instruments enable the operation of this beamline as an automated MX beamline specialized in X-ray fragment screening. This beamline can collect more than 400 data sets a day without human intervention, and a difference map can be automatically calculated by using the data processing pipeline for ligand or fragment identification.

scholarly journals Physical sciences at Diamond: past achievements and future opportunities

2015 ◽  
Vol 373 (2036) ◽  
pp. 20130150 ◽  
Author(s):  
D. F. McMorrow
Keyword(s):  
Light Source ◽  
Third Generation ◽  
Physical Sciences ◽  
Personal View ◽  
X Ray ◽  
The Third ◽  
The Uk

The start of user operation at the Diamond Light Source in January 2007 marks a major milestone for the physical sciences in the UK. The routine delivery to the UK community of ultra-bright X-ray beams from the third-generation source has provided us with capabilities that were available previously only at international sources, and indeed has created some that are unique. Here, a personal view is given of some of the achievements to date, and possible future opportunities outlined.

The Canadian Light Source — History and scientific prospects

2004 ◽  
Vol 82 (6) ◽  
pp. 1028-1042 ◽  
Author(s):  
G M Bancroft
Keyword(s):  
Light Source ◽  
X Rays ◽  
X Ray ◽  
The Third ◽  
Scientific Disciplines ◽  
The World ◽  
History Of ◽  
Synchrotron Light ◽  
Under Construction ◽  
The University

The Canadian Light Source (CLS) in Saskatoon has been under construction for the last 4 years, and will be producing a number of very intense beams of far-IR, IR, soft and hard X-rays in 2004 for use by several hundred Canadian scientists in chemistry, surface and material science, and a host of other scientific disciplines. The CLS will dramatically enhance the Canadian spectroscopic tradition that Gerhard Herzberg help create. I begin this article (from my 2002 CIC Montreal Medal lecture) with an overview of the history of SR in Canada, beginning in 1972 with the first Canadian synchrotron workshop organized at the University of Western Ontario by Bill McGowan, and attended by Dr. Herzberg. The CLS facility is then described, along with the properties of the first and second set of beamlines to be built at the CLS. These SR beams, in the IR and X-ray regions from the third generation CSL ring, will be competitive in brightness and intensity with the best beamlines in the world for most applications. Finally, some of the present Canadian SR research at foreign SR sources is described across the entire SR spectrum. All known spectroscopic and diffraction experiments are dramatically enhanced with SR; and SR opens up new areas of spectroscopy, microscopy, and spectromicroscopy that cannot be studied with any other source of radiation.Key words: synchrotron light, X-rays, infrared, spectroscopy.

scholarly journals Robotic sample changers for macromolecular X-ray crystallography and biological small-angle X-ray scattering at the National Synchrotron Light Source II. Corrigendum

2022 ◽  
Vol 29 (1) ◽  
Author(s):  
Edwin O. Lazo ◽  
Stephen Antonelli ◽  
Jun Aishima ◽  
Herbert J. Bernstein ◽  
Dileep Bhogadi ◽  
...  
Keyword(s):  
Light Source ◽  
Small Angle ◽  
National Synchrotron Light Source ◽  
X Ray ◽  
X Ray Crystallography ◽  
X Ray Scattering ◽  
Synchrotron Light ◽  
Ray Scattering

A correction in the paper by Lazo et al. [(2021). J. Synchrotron Rad. 28, 1649–1661] is made.

scholarly journals Updated plans for DIAMOND, a new X-ray light source for the UK

2002 ◽  
Author(s):  
V.P. Suller ◽  
J.A. Clarke ◽  
J.B. Fitzgerald ◽  
H.L. Owen ◽  
M.W. Poole ◽  
...  
Keyword(s):  
Light Source ◽  
X Ray ◽  
The Uk

scholarly journals Discovery of Novel Druggable Sites on Zika Virus NS3 Helicase Using X-ray Crystallography-Based Fragment Screening

2018 ◽  
Vol 19 (11) ◽  
pp. 3664 ◽  
Author(s):  
Ali Munawar ◽  
Steven Beelen ◽  
Ahmad Munawar ◽  
Eveline Lescrinier ◽  
Sergei Strelkov
Keyword(s):  
Zika Virus ◽  
Dissociation Constants ◽  
Global Public Health ◽  
Human Pathogens ◽  
Allosteric Site ◽  
Replication Complex ◽  
X Ray ◽  
X Ray Crystallography ◽  
Fragment Screening ◽  
Atomic Precision

The flavivirus family contains several important human pathogens, such as Zika virus (ZIKV), dengue, West Nile, and Yellow Fever viruses, that collectively lead to a large, global disease burden. Currently, there are no approved medicines that can target these viruses. The sudden outbreak of ZIKV infections in 2015–2016 posed a serious threat to global public health. While the epidemic has receded, persistent reservoirs of ZIKV infection can cause reemergence. Here, we have used X-ray crystallography-based screening to discover two novel sites on ZIKV NS3 helicase that can bind drug-like fragments. Both sites are structurally conserved in other flaviviruses, and mechanistically significant. The binding poses of four fragments, two for each of the binding sites, were characterized at atomic precision. Site A is a surface pocket on the NS3 helicase that is vital to its interaction with NS5 polymerase and formation of the flaviviral replication complex. Site B corresponds to a flexible, yet highly conserved, allosteric site at the intersection of the three NS3 helicase domains. Saturation transfer difference nuclear magnetic resonance (NMR) experiments were additionally used to evaluate the binding strength of the fragments, revealing dissociation constants (KD) in the lower mM range. We conclude that the NS3 helicase of flaviviruses is a viable drug target. The data obtained open opportunities towards structure-based design of first-in-class anti-ZIKV compounds, as well as pan-flaviviral therapeutics.

scholarly journals Determination of X-ray flux using silicon pin diodes

2009 ◽  
Vol 16 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Robin L. Owen ◽  
James M. Holton ◽  
Clemens Schulze-Briese ◽  
Elspeth F. Garman
Keyword(s):  
Light Source ◽  
Energy Deposition ◽  
Photon Flux ◽  
Macromolecular Crystallography ◽  
Pin Diodes ◽  
Web Based ◽  
X Ray ◽  
Swiss Light Source ◽  
Flux Incident

Accurate measurement of photon flux from an X-ray source, a parameter required to calculate the dose absorbed by the sample, is not yet routinely available at macromolecular crystallography beamlines. The development of a model for determining the photon flux incident on pin diodes is described here, and has been tested on the macromolecular crystallography beamlines at both the Swiss Light Source, Villigen, Switzerland, and the Advanced Light Source, Berkeley, USA, at energies between 4 and 18 keV. These experiments have shown that a simple model based on energy deposition in silicon is sufficient for determining the flux incident on high-quality silicon pin diodes. The derivation and validation of this model is presented, and a web-based tool for the use of the macromolecular crystallography and wider synchrotron community is introduced.

Sign in / Sign up

Export Citation Format

Share Document