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A fast and fully automated solution for Lipidic Cubic Phase (LCP) screening using mosquito LCP
Joby Jenkins1, Patricia Edwards2, Rob Lewis1and Joanne Franklin1

Membrane proteins, such as G-protein-coupled receptors, are known to be much more difficult to purify and crystallise than soluble proteins due to their native environment within the lipid bilayer of the cell membrane. The in meso (lipidic cubic phase or LCP) crystallisation technique has revolutionised the process of crystallising membrane proteins. This method utilises highly viscous lipid mesophases to contain the membrane proteins for crystallisation.

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mosquito® Crystal: Fast, reliable automation of Protein Crystallization drop set-up
Joby Jenkins, David Smith, Chloe Carter, Wendy Gaisford

Automation of protein crystallography screening has contributed significantly to the rapid progress of crystallography based structural biology. Automation allows samples to be screened using smaller volumes of both protein and screen solutions, reducing costs and saving valuable protein. Additional benefits include increased throughput and accuracy. One of the challenges to automating this process is the necessity to accurately pipette solutions of varying viscosities

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Analysis of overall success of robotic crystallization
I. Ivanovic, H. M. Baker, J. S. Lott and E. N. Baker

A total of about 140 different proteins have been commissioned and 62 have been crystallized with a quality suitable for X-ray diffraction (45%). On a per-drop basis, 300 crystallization experiments have been successful, representing an over¬all success rate of 3%. PEG 3350 was the precipitant for 20, making it the single most successful crystallization agent.

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Strategies for expression and solubility analysis

Production of soluble protein is one of the major bottlenecks that precede crystallographic studies.During the last years several techniques and strategies have been developed to address this problem. However, many of them imply an economical cost and technologies that are not always available. We will describe a general plan for protein solubility analysis by using a combination of four different but complementary strategies. In this plan, different constructs of a protein interest are designed

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Automating Microseeding Protein Crystallography Set-ups Using Mosquito
Joby Jenkins, David Smith, Rob Lewis, Chloe Carter

Crystallising proteins, required for structure determination by X-ray diffraction, is a difficult and labour-intensive task. The mosquito liquid handler (TTP LabTech) is ideally suited to automating the complex set-ups required for microseeding due to its precide handling of extremely low volumes of even viscous solutions, and its ability to perform multiple aspirations and dispenses with each pipette.

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Automated Single Crystal Structure Determination - A Tool for Synthetic Chemists?
Bernd Hinrichsen, Martin Adam, Michael Carr, Dieter Schollmeyer,

During recent years large improvements in software functionality and its ease-of-use have made single crystal X-ray structure determination easier than ever. These days most structures can be measured, processed, solved and refined using well selected defaults with no or little crystallographic knowledge. Recently, microfocus sources and CCD detectors both air-cooled, have entered the marketplace. Combining these innovations with an automated sample loader and an intelligent graphical user inte

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Advances in Crystallographic Hardware for Structural Biology
Matthew Benning and Michael Ruf, Bruker AXS Inc., East Cheryl Parkway

The number of life science investigators utilizing crystallography in their research increases every year. Synchrotrons are an invaluable resource for structural work but not everyone has unlimited access to a beamline. In-house diffraction systems complement synchrotron access and can provide increased productivity in the home lab. In recent years, the performance and versatility of in-house systems has greatly improved. The enhanced performance allows data collection on demanding projects such

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MED-SuMo and MED-Hybridise: exploit all PDB macromolecule structures to design/optimize innovative leads
Moriaud F., Oguievetskaia K., Adcock S.A., Vorotynsev A.M., Martin L., Doppelt-Azeroual O. and Delfaud F.

Obtaining structural information on fragment-protein target is a key factor and also a major limitation. We’ve used MED-SuMo and MED-Hybridise to query and mine the PDB seeking for similar interaction surfaces. MED-portions were used to design novel scaffolds (GPCR) and decorate a given scaffold (kinase). We have analysed the scaffolds in regard to their diversity, their presence in PubChem, PDB and other libraries.

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Phase Diagram Visualization via Continuously-Fed Crystallization: Experiments and Model
Masano Sugiyama and Victor Barocas

A continuously-fed crystallization chamber is manufactured to allow phase diagram visualization. This microfluidic system allows the experimenter to screen a large range of salt and protein concentrations in one experiment. This allows the experimenter to predict the protein phase diagram in a single experiment. A continuous-feed crystallization chamber has been successfully fabricated and characterized in terms of its flow profile, and has successfully predicted the phase diagram for lysozyme.

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Scientific News
Human Astrovirus Structure Could Lead to Therapies, Vaccines
Study shows where neutralizing antibody binds to human astrovirus, a leading cause of viral diarrhoea in children, elderly, and the immune-compromised.
Drug Design Strategy to Improve Breast Cancer Treatment
Scientists develop novel structure-based drug design strategy aimed at altering the basic landscape of hormone-driven breast cancer treatment.
Crystals, Super Magnets in Drug Discovery
Scientists have produced larger superparamagnetic crystals that could revolutionise drug delivery.
Peer Review is in Crisis, But Should be Fixed, Not Abolished
After the time to get the science done, peer review has become the slowest step in the process of sharing studies, and some scientists have had enough.
Snapshots of Chemical Flipping a Biological Switch
X-ray laser gets first real-time snapshots of a chemical flipping a biological switch, opening new path to understanding how RNA works.
Uncovering Elusive Proteins
Researchers have determined the complete structure of elusive proteins, known as tetraspanins, for the first time.
Cannabinoid Receptor Structure Revealed
Scientists provided a detailed view of the primary molecule through which cannabinoids exert their effects on the brain. The findings might help guide the design of more targeted medicines with fewer side effects.
Alzheimer’s Treatment Moves a Step Closer
Merck scientists have reported the discovery of verubecestat, a structurally unique, orally bioavailable small molecule that has been shown to target the most visible sign of the disease in the brain.
Study Unocovers Cancer-Linked Protein’s Associates
Researchers have developed a new list of nearly 100 potential partners of a cancer-linked enzyme by studying its interactions with other proteins.
Scientists Uncover Why Hepatitis C Vaccine is Difficult to Make
Scientists have uncovered one reason why a successful hepatitis C vaccine continues to be elusive.
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