A5028825393- Enzyme Structure and Function
- Protein Structure and Dynamics
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Advanced Electron Microscopy Techniques and Applications
- Advanced X-ray Imaging Techniques
- Legionella and Acanthamoeba research
- ATP Synthase and ATPases Research
- Mass Spectrometry Techniques and Applications
- Bacterial Genetics and Biotechnology
- Geophysical and Geoelectrical Methods
- Synthesis and biological activity
- Photosynthetic Processes and Mechanisms
- Nuclear Physics and Applications
- Crystal structures of chemical compounds
- Advanced NMR Techniques and Applications
- Scientific Research and Discoveries
- Machine Learning in Materials Science
- Advanced Proteomics Techniques and Applications
- Smart Agriculture and AI
- Gaze Tracking and Assistive Technology
- NMR spectroscopy and applications
- Synthesis of Organic Compounds
- Advanced Materials and Mechanics
- Synthesis of heterocyclic compounds
Leiden University Medical Center
2022-2024
Leiden University
2005-2018
Heptares Therapeutics (United Kingdom)
2016
European Science Foundation
2009
Daresbury Laboratory
2007
Slovak University of Technology in Bratislava
2004-2006
University of Cambridge
2005
Wellcome Trust
2005
Lawrence Berkeley National Laboratory
2005
This paper describes various components of the macromolecular crystallographic refinement program REFMAC5, which is distributed as part CCP4 suite. REFMAC5 utilizes different likelihood functions depending on diffraction data employed (amplitudes or intensities), presence twinning and availability SAD/SIRAS experimental data. To ensure chemical structural integrity refined model, offers several classes restraints choices model parameterization. Reliable models at resolutions least low 4 Å...
The CCP4 (Collaborative Computational Project, Number 4) software suite for macromolecular structure determination by X-ray crystallography groups brings together many programs and libraries that, means of well established conventions, interoperate effectively without adhering to strict design guidelines. Because this inherent flexibility, users are often presented with diverse, even divergent, choices solving every type problem. Recently, introduced CCP4i2, a modern graphical interface...
The Collaborative Computational Project No. 4 (CCP4) is a UK-led international collective with mission to develop, test, distribute and promote software for macromolecular crystallography. CCP suite multiplatform collection of programs brought together by familiar execution routines, set common libraries graphical interfaces. has experienced several considerable changes since its last reference article, involving new infrastructure, original This which intended as general literature citation...
Determining new protein structures from X-ray diffraction data at low resolution or with a weak anomalous signal is difficult and often an impossible task. Here we propose multivariate algorithm that simultaneously combines the structure determination steps. In tests on over 140 real sets bank, show this combined approach can automatically build models where current algorithms fail, including anisotropically diffracting 3.88 Å RNA polymerase II set. The method seamlessly automates process,...
Nowadays, progress in the determination of three-dimensional macromolecular structures from diffraction images is achieved partly at cost increasing data volumes. This due to deployment modern high-speed, high-resolution detectors, increased complexity and variety crystallographic software, use extensive databases high-performance computing. limits what can be accomplished with personal, offline, computing equipment terms both productivity maintainability. There also an issue long-term...
The incorporation of prior phase information into a maximum-likelihood formalism has been shown to strengthen model refinement. However, the currently available likelihood refinement target using shortcomings; `phased' considers experimental indirectly and statically in form Hendrickson–Lattman coefficients. Furthermore, current implicitly assumes that is independent calculated structure factor. This paper describes derivation multivariate function overcomes these shortcomings directly...
For its first release in 2004, CRANK was shown to effectively detect and phase anomalous scatterers from single-wavelength diffraction data. Since then, has been significantly improved many more structures can be built automatically with single- or multiple-wavelength single isomorphous replacement scattering Here, the new algorithms that have developed led these substantial improvements are discussed CRANK's performance on over 100 real data sets is shown. The latest version of freely...
Determining macromolecular structures from X-ray data with resolution worse than 3 Å remains a challenge. Even if related starting model is available, its incompleteness or bias together low observation-to-parameter ratio can render the process unsuccessful very time-consuming. Yet, many biologically important macromolecules, especially large assemblies, membrane proteins and receptors, tend to provide crystals that diffract resolution. A new algorithm tackle this problem presented uses...
Density modification is a standard technique in macromolecular crystallography that can significantly improve an initial electron-density map. To obtain optimal results, the and density-modified map are combined. Current methods assume these two maps independent propagate information its accuracy indirectly through previously determined coefficients. A multivariate equation has been derived no longer assumes independence between map, considers observed diffraction data directly refines...
Thus far, the application of phase-retrieval methods in crystallography has mainly been aimed at variants charge flipping or structure-factor flipping. In this work, relaxed averaged alternating reflections (RAAR) algorithm is applied to determine anomalously scattering substructures from single-wavelength anomalous diffraction (SAD) data macromolecules. The implemented a new program, PRASA , and shown significantly outperform determining on test sample 169 SAD sets with resolutions up 3.88 Å.
The experimental charge density of the Ni II complex Schiff base ( S )- N -(2-benzoylphenyl)-1-benzylprolinamide and glycine was derived from high-resolution single-crystal X-ray diffraction data (λ = 0.5604 Å) at low temperature (100 K) with synchrotron radiation beamline F1 using a CCD area detector. central atom is pseudo-square-planar coordinated by three atoms [1.9414 (3), 1.8559 (3) 1.8533 Å] one O [1.8620 (4) Å]. N(1) 0.359 Å above plane defined Ni(1), N(2) N(3). d -orbital population...
A likelihood function based on the multivariate probability distribution of all observed structure-factor amplitudes from a single isomorphous replacement with anomalous scattering experiment has been derived and implemented for use in substructure refinement phasing as well macromolecular model refinement. Efficient calculation multidimensional integration required evaluation achieved by approximations function's properties. The both protein building iterative was essential successful...
Page s 34pre-defined number of core objects, so that each structural motif (domain) contained in the structure is represented by one such core.Rather than follow a simplistic approach assigning known domain structures to segment low-resolution map, this work we target more general unbiased shape identification terms domains.No detailed knowledge about composition lowresolution complex required.A pattern-recognition comparative analysis which makes use 3 rd order moment invariants [1] and...
Previously, the direct use of prior phase information from a single-wavelength anomalous diffraction (SAD) experiment with multivariate likelihood function applied to automated model building iterative refinement has been proposed [Skubák et al. (2004), Acta Cryst. D60, 2196-2201]. In this approach, experimental data is used in derive maximum-likelihood formalism and provided more theoretically valid way incorporating compared current approaches. present work, SAD that directly uses tested...
The incorporation of prior phase information in a maximum likelihood formalism has been shown to strengthen model refinement.However, the currently available refinement target using shortcomings: considers experimental indirectly and statically form Hendrickson-Lattman coeffcients.Furthermore, current implicitly assumes that is independent from calculated structure factor.We have derived multivariate function overcomes these shortcomings directly incorporates single wavelength anomalous...
Density modification often suffers from an overestimation of phase quality, as seen by escalated figures merit. A new cross-validation-based method to address this estimation bias applying a bias-correction parameter 'β' maximum-likelihood phase-combination functions is proposed. In tests on over 100 single-wavelength anomalous diffraction data sets, the shown produce much more reliable merit and improved electron-density maps. Furthermore, significantly better results are obtained in...
When solving a structure of protein from single-wavelength anomalous diffraction X-ray data, the initial phases obtained by phasing an anomalously scattering substructure usually need to be improved iterated electron-density modification. In this manuscript, use convolutional neural networks (CNNs) for segmentation experimental maps is proposed. The results reported demonstrate that CNN with U-net architecture, trained on several thousands generated mainly using data Protein Data Bank in...
To determine a substructure from single-wavelength anomalous diffraction (SAD) data using Patterson or direct methods, the substructure-factor amplitude (| F |) is first estimated. Currently, absolute value of Bijvoet difference widely used as an estimate | values for SAD data. Here, equation derived multivariate statistics and tested that takes into account correlation between observed positive ( + ) negative − Friedel pairs along with measurement errors in The estimation has been...
SPACE [1] and beamline control software BSS [2].For smooth communication with distant users via the Internet, we have newly developed data management system D-Cha (Database for Crystallography Home-lab Arrangements) which mediates between SPring-8 beamlines.D-Cha provides GUI to deposit experimental conditions samples browse / download collected on web browser.The mail-in has been operated Structural Genomics Project at RIKEN II (BL26B2) since September 2005.Then presented public Biology III...
The absolute configuration of the title compound, C 25 H 28 N 2 O 4 S, has been determined. molecules are interconnected by weak C—H...O hydrogen bonds. 1,4-dihydropyridine (1,4-DHP) ring adopts usual shallow boat conformation. thiophene is nearly planar.
The major current bottleneck for macromolecular structure solution from SAD data is determination of positions the anomalously scattering atoms.The programs substructure are usually based on "direct" methods developed small molecules, obtaining phase estimates relations between intensities and phases reflections or Patterson function.From a more general point view, X-ray crystallography problem belongs to class non-linear non-convex inverse problems.Although no known this problems, they have...