- Cancer Biology & Biomarkers
- Chromatography & Mass Spectrometry
- Contract Research, Clinical Trials and Outsourcing
- Drug Discovery
- Drug Targets
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Protein crystallography - Articles and news items
Issue 5 2014 / 29 October 2014 / Dave Elder, GlaxoSmithKline and JPAG
Crystallography is the science underpinning crystallisation, as well as a basic understanding of atomic arrangement within solids and their resulting structures. The United Nations announced that 2014 would be the International Year of Crystallography (IYCr2014). IYCr2014 commemorates the 100th anniversary of X-ray diffraction according to Bragg’s Law (celebrated by the 1915 Nobel Prize for Physics), and the 400th anniversary of ice crystal symmetry by Johannes Kepler, who identified the critical role of symmetry in the solid state…
Protein crystallography is an integral component of the structure-guided drug discovery process. Rapid access to structural information about drug targets as well as bound ligands has been pivotal in accelerating lead identification and optimisation processes. While automation and robotics have been employed at every stage along the gene-to-structure path, significant challenges remain in increasing successful outcomes and in reduction of timelines. Advances in high through-put technologies to automate protein expression and crystallisation, the two weakest links in the gene-to-structure process chain, are beginning to address these issues. This article will highlight the importance of rapid structure determination of protein-ligand complexes in lead optimisation, and describe recent developments towards overcoming these bottlenecks.
Issue 3 2007 / 23 May 2007 / Julie Wilson, York Structural Biology Laboratory, Department of Chemistry, University of Heslington, York, UK
The findings of many crystallisation experiments are required in order to identify conditions that will produce diffraction quality crystals. The use of robots has increased the number of experiments performed in most laboratories and, in structural genomics centres, tens of thousands of experiments can be produced every day. As each experiment must be assessed regularly over a period of time, visual inspection is becoming increasingly impractical and automated imaging systems are now available to record the results; the aim of this research is the development of software to analyse and classify images from crystallisation trials.
Protein crystallography has been embraced by the pharmaceutical industry to accelerate and rationalise the drug development process. In this role, success rates, throughput and turnaround times have become key competitive factors, and nearly every stage in the protein crystallography process has been targeted for automation using robotics and advanced software. However, it remains a challenge to combine available technologies, information infrastructure and work-flow protocols into a high throughput protein crystallography pipeline that takes account of the specific objectives and resources of an organisation. This article reviews process outlines and key decision making criteria to assist with the selection of a high throughput protein crystallography strategy.
The Structural Genomics Consortium (SGC) is an internationally funded collaboration with sites in three countries and a three-year goal of solving the 3-dimensional structures of more than 380 human proteins with particular medical relevance, and placing them in the public domain without restrictions. The structures should prove an invaluable resource for research into the proteins’ functions and their use as targets for therapeutic intervention; in this the SGC is a successor to the Human Genome Project (HGP). The SGC has benefited from adopting existing, commercialised robotics, and is subsequently working with vendors to adjust performance with its needs.
Protein crystallography has a key role to play in a project that is making a significant contribution to understanding human diseases. The Structural Genomics Consortium (SGC) has already achieved one landmark, and looks set to continue in a similar vein. Tim Lloyd spoke with Alexey Bochkarev Ph.D., Principal Investigator, Crystallography, at SGC Toronto, to learn more.
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