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Gwyndaf Evans

Bio: Gwyndaf Evans is an academic researcher from Franklin Institute. The author has contributed to research in topics: Beamline & Protein crystallization. The author has an hindex of 32, co-authored 93 publications receiving 4342 citations. Previous affiliations of Gwyndaf Evans include Laboratory of Molecular Biology & Max Planck Society.


Papers
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Journal ArticleDOI
TL;DR: A new X-ray diffraction data-analysis package is presented with a description of the algorithms and examples of its application to biological and chemical crystallography.
Abstract: The DIALS project is a collaboration between Diamond Light Source, Lawrence Berkeley National Laboratory and CCP4 to develop a new software suite for the analysis of crystallographic X-ray diffraction data, initially encompassing spot finding, indexing, refinement and integration. The design, core algorithms and structure of the software are introduced, alongside results from the analysis of data from biological and chemical crystallography experiments.

733 citations

Journal ArticleDOI
TL;DR: These structures provide a model for enterovirus uncoating in which the VP1 GH loop acts as an adaptor-sensor for cellular receptor attachment, converting heterologous inputs to a generic uncoated mechanism, highlighting new opportunities for therapeutic intervention.
Abstract: Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease and death. No vaccine or antiviral therapy is available. High-resolution structural analysis of the mature virus and natural empty particles shows that the mature virus is structurally similar to other enteroviruses. In contrast, the empty particles are markedly expanded and resemble elusive enterovirus-uncoating intermediates not previously characterized in atomic detail. Hydrophobic pockets in the EV71 capsid are collapsed in this expanded particle, providing a detailed explanation of the mechanism for receptor-binding triggered virus uncoating. These structures provide a model for enterovirus uncoating in which the VP1 GH loop acts as an adaptor-sensor for cellular receptor attachment, converting heterologous inputs to a generic uncoating mechanism, highlighting new opportunities for therapeutic intervention.

359 citations

Journal ArticleDOI
21 Nov 2016-Nature
TL;DR: Ammonia, a water analogue, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S2 and S3 states, and this approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O–O bond formation mechanisms.
Abstract: Light-induced oxidation of water by photosystem II (PS II) in plants, algae and cyanobacteria has generated most of the dioxygen in the atmosphere. PS II, a membrane-bound multi-subunit pigment protein complex, couples the one-electron photochemistry at the reaction centre with the four-electron redox chemistry of water oxidation at the Mn4CaO5 cluster in the oxygen-evolving complex (OEC). Under illumination, the OEC cycles through five intermediate S-states (S0 to S4), in which S1 is the dark-stable state and S3 is the last semi-stable state before O-O bond formation and O2 evolution. A detailed understanding of the O-O bond formation mechanism remains a challenge, and will require elucidation of both the structures of the OEC in the different S-states and the binding of the two substrate waters to the catalytic site. Here we report the use of femtosecond pulses from an X-ray free electron laser (XFEL) to obtain damage-free, room temperature structures of dark-adapted (S1), two-flash illuminated (2F; S3-enriched), and ammonia-bound two-flash illuminated (2F-NH3; S3-enriched) PS II. Although the recent 1.95 A resolution structure of PS II at cryogenic temperature using an XFEL provided a damage-free view of the S1 state, measurements at room temperature are required to study the structural landscape of proteins under functional conditions, and also for in situ advancement of the S-states. To investigate the water-binding site(s), ammonia, a water analogue, has been used as a marker, as it binds to the Mn4CaO5 cluster in the S2 and S3 states. Since the ammonia-bound OEC is active, the ammonia-binding Mn site is not a substrate water site. This approach, together with a comparison of the native dark and 2F states, is used to discriminate between proposed O-O bond formation mechanisms.

311 citations

Journal ArticleDOI
TL;DR: A Fortran program CHOOCH as discussed by the authors derives experimental values of the anomalous-scattering factors f′′ and f′ from X-ray fluorescence spectra, which aids the decision-making process in macromolecular crystallographic experiments where optimal wavelength selection is required.
Abstract: A Fortran program CHOOCH, which derives experimental values of the anomalous-scattering factors f′′ and f′ from X-ray fluorescence spectra, is described. The program assumes knowledge of theoretical values for the imaginary term, f′′, of the anomalous-scattering factor away from the absorption edge to scale the experimental fluorescence spectrum and thus derive values of f′′ near the absorption edge, where tabular data are inappropriate. The Kramers–Kronig relation is used to calculate the real part, f′, of the anomalous-scattering factor. The program aids the decision-making process in macromolecular crystallographic experiments where optimal wavelength selection is required. Magnitudes of f′ and f′′ at selected wavelengths can later be used as starting values for heavy-atom refinement with crystallographic phasing programs.

264 citations

Journal ArticleDOI
08 Jan 2004-Nature
TL;DR: The crystal structures of human vinculin in its inactive and talin-activated states support a model whereby Vh functions as a domain that undergoes marked structural changes that allow Vinculin to direct cytoskeletal assembly in focal adhesions and adherens junctions.
Abstract: Vinculin is a conserved component and an essential regulator of both cell-cell (cadherin-mediated) and cell-matrix (integrin-talin-mediated focal adhesions) junctions, and it anchors these adhesion complexes to the actin cytoskeleton by binding to talin in integrin complexes or to alpha-actinin in cadherin junctions. In its resting state, vinculin is held in a closed conformation through interactions between its head (Vh) and tail (Vt) domains. The binding of vinculin to focal adhesions requires its association with talin. Here we report the crystal structures of human vinculin in its inactive and talin-activated states. Talin binding induces marked conformational changes in Vh, creating a novel helical bundle structure, and this alteration actively displaces Vt from Vh. These results, as well as the ability of alpha-actinin to also bind to Vh and displace Vt from pre-existing Vh-Vt complexes, support a model whereby Vh functions as a domain that undergoes marked structural changes that allow vinculin to direct cytoskeletal assembly in focal adhesions and adherens junctions. Notably, talin's effects on Vh structure establish helical bundle conversion as a signalling mechanism by which proteins direct cellular responses.

252 citations


Cited by
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Christopher M. Bishop1
01 Jan 2006
TL;DR: Probability distributions of linear models for regression and classification are given in this article, along with a discussion of combining models and combining models in the context of machine learning and classification.
Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

10,141 citations

Journal ArticleDOI
10 Mar 1970

8,159 citations

01 Aug 2000
TL;DR: Assessment of medical technology in the context of commercialization with Bioentrepreneur course, which addresses many issues unique to biomedical products.
Abstract: BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

4,833 citations

Journal ArticleDOI
TL;DR: A new approach that integrates data collection, data reduction, phasing and model building significantly accelerates the process of structure determination and on average minimizes the number of data sets and synchrotron time required for structure solution.
Abstract: A new approach that integrates data collection, data reduction, phasing and model building significantly accelerates the process of structure determination and on average minimizes the number of data sets and synchrotron time required for structure solution. Initial testing of the HKL-3000 system (the beta version was named HKL-2000_ph) with more than 140 novel structure determinations has proven its high value for MAD/SAD experiments. The heuristics for choosing the best computational strategy at different data resolution limits of phasing signal and crystal diffraction are being optimized. The typical end result is an interpretable electron-density map with a partially built structure and, in some cases, an almost complete refined model. The current development is oriented towards very fast structure solution in order to provide feedback during the diffraction experiment. Work is also proceeding towards improving the quality of phasing calculation and model building.

1,791 citations