J. Appl. Cryst.の発刊に際して
10 Mar 1970-Vol. 12, Iss: 1, pp 1-1
About: The article was published on 1970-03-10 and is currently open access. It has received 8159 citations till now.
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TL;DR: 2′-F-modified nucleotides are well tolerated in the guide and passenger siRNA strands and the corresponding duplexes lack immunostimulatory effects, enhance nuclease resistance and display improved efficacy in vitro and in vivo compared with unmodified siRNAs.
Abstract: Various chemical modifications are currently being evaluated for improving the efficacy of short interfering RNA (siRNA) duplexes as antisense agents for gene silencing in vivo. Among the 2'-ribose modifications assessed to date, 2'deoxy-2'-fluoro-RNA (2'-F-RNA) has unique properties for RNA interference (RNAi) applications. Thus, 2'-F-modified nucleotides are well tolerated in the guide (antisense) and passenger (sense) siRNA strands and the corresponding duplexes lack immunostimulatory effects, enhance nuclease resistance and display improved efficacy in vitro and in vivo compared with unmodified siRNAs. To identify potential origins of the distinct behaviors of RNA and 2'-F-RNA we carried out thermodynamic and X-ray crystallographic analyses of fully and partially 2'-F-modified RNAs. Surprisingly, we found that the increased pairing affinity of 2'-F-RNA relative to RNA is not, as commonly assumed, the result of a favorable entropic contribution ('conformational preorganization'), but instead primarily based on enthalpy. Crystal structures at high resolution and osmotic stress demonstrate that the 2'-F-RNA duplex is less hydrated than the RNA duplex. The enthalpy-driven, higher stability of the former hints at the possibility that the 2'-substituent, in addition to its important function in sculpting RNA conformation, plays an underappreciated role in modulating Watson-Crick base pairing strength and potentially π-π stacking interactions.
150 citations
TL;DR: An automation pipeline for macromolecular structure solution by molecular replacement with a special emphasis on the discovery and preparation of a large number of search models is described.
Abstract: A novel automation pipeline for macromolecular structure solution by molecular replacement is described. There is a special emphasis on the discovery and preparation of a large number of search models, all of which can be passed to the core molecular-replacement programs. For routine molecular-replacement problems, the pipeline automates what a crystallographer might do and its value is simply one of convenience. For more difficult cases, the pipeline aims to discover the particular template structure and model edits required to produce a viable search model and may succeed in finding an efficacious combination that would be missed otherwise. An overview of MrBUMP is given and some recent additions to its functionality are highlighted.
149 citations
Cites methods from "J. Appl. Cryst.の発刊に際して"
...The fourth method uses the program Chainsaw (Stein, 2008), which uses an alignment extracted from the previous multiple alignment step....
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...In the ‘twilight zone’ where the alignment is not necessarily reliable, it may be necessary to try different alignments in the Chainsaw step, either from the same program or from different programs....
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...The multiple alignment step aligns the five template chains against the target sequence and pairwise alignments are extracted for use in Chainsaw....
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...For example, 1ogk_B_CHNSAW refers to chain B of 1ogk prepared using the program Chainsaw....
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...MOLREP and Chainsaw are similar in purpose, but differ in the details of the alignment used and the extent of side-chain truncation....
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TL;DR: The principles of one-dimensional FFT-based autoindexing of diffraction images are described and a procedure for indexing multiple lattices as implemented in iMosflm is presented.
Abstract: An overview of autoindexing diffraction images based on one-dimensional fast Fourier transforms is presented. The implementation of the algorithm in the Mosflm/iMosflm program suite is described with a discussion of practical issues that may arise and ways of assessing the success or failure of the procedure. Recent developments allow indexing of images that show multiple lattices, and several examples demonstrate the success of this approach in real cases.
148 citations
Cites background or methods from "J. Appl. Cryst.の発刊に際して"
...…vectors are used in indexing (Kabsch, 1993), while other widely used software suites use an approach based on a fast Fourier transform (FFT) of the reciprocal-space vectors either in three dimensions (Campbell, 1998; Otwinowski & Minor, 2001) or in one dimension (Steller et al., 1997)....
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...…autoindexing algorithms did require knowledge of (approximate) unit-cell parameters (Vriend & Rossmann, 1987; Kabsch, 1988), but these were rapidly superseded by improved procedures where this was not required (Kim, 1989; Higashi, 1990; Kabsch, 1993; Steller et al., 1997; Sauter et al., 2004)....
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...The one-dimensional FFT-based indexing algorithm has been described in detail elsewhere (Steller et al., 1997; Powell, 1999), but the general principles involved are summarized here....
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...The distortion penalties are calculated as in the DPS program (Steller et al., 1997), but for completeness this is described in detail below....
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...The indexing provides a description of the crystal unit-cell parameters and the orientation of the crystal relative to a laboratory frame....
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TL;DR: The protocols of the crystalline sponge method, particularly those in the soaking, data collection and refinement processes, are considerably improved to give reliable structural information.
148 citations
Cites methods from "J. Appl. Cryst.の発刊に際して"
...After obtaining an initial structure for refinement using a standard program [SHELXT, (Sheldrick, 2015), SHELXS (Sheldrick, 2008), SIR (Burla et al., 2015), or SUPERFLIP (Palatinus & Chapuis, 2007)], the refinement of the host framework should be performed first....
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TL;DR: The implied two orders of magnitude efficiency gain as compared to currently available techniques in this regime paves the way for unprecedented structural investigations of complex sample systems of interest for material science in a vast range of fields.
Abstract: Grating interferometer based imaging with X-rays and neutrons has proven to hold huge potential for applications in key research fields conveying biology and medicine as well as engineering and magnetism, respectively. The thereby amenable dark-field imaging modality implied the promise to access structural information beyond reach of direct spatial resolution. However, only here a yet missing approach is reported that finally allows exploiting this outstanding potential for non-destructive materials characterizations. It enables to obtain quantitative structural small angle scattering information combined with up to 3-dimensional spatial image resolution even at lab based x-ray or at neutron sources. The implied two orders of magnitude efficiency gain as compared to currently available techniques in this regime paves the way for unprecedented structural investigations of complex sample systems of interest for material science in a vast range of fields.
146 citations
Cites background from "J. Appl. Cryst.の発刊に際して"
...Due to the modulation geometry a grating set-up is sensitive to SAS in one dimension only....
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References
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TL;DR: The goals of the PDB are described, the systems in place for data deposition and access, how to obtain further information and plans for the future development of the resource are described.
Abstract: The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules. This paper describes the goals of the PDB, the systems in place for data deposition and access, how to obtain further information, and near-term plans for the future development of the resource.
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TL;DR: New features added to the refinement program SHELXL since 2008 are described and explained.
Abstract: The improvements in the crystal structure refinement program SHELXL have been closely coupled with the development and increasing importance of the CIF (Crystallographic Information Framework) format for validating and archiving crystal structures. An important simplification is that now only one file in CIF format (for convenience, referred to simply as `a CIF') containing embedded reflection data and SHELXL instructions is needed for a complete structure archive; the program SHREDCIF can be used to extract the .hkl and .ins files required for further refinement with SHELXL. Recent developments in SHELXL facilitate refinement against neutron diffraction data, the treatment of H atoms, the determination of absolute structure, the input of partial structure factors and the refinement of twinned and disordered structures. SHELXL is available free to academics for the Windows, Linux and Mac OS X operating systems, and is particularly suitable for multiple-core processors.
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TL;DR: CCP4mg is a project that aims to provide a general-purpose tool for structural biologists, providing tools for X-ray structure solution, structure comparison and analysis, and publication-quality graphics.
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TL;DR: The PHENIX software for macromolecular structure determination is described and its uses and benefits are described.
Abstract: Macromolecular X-ray crystallography is routinely applied to understand biological processes at a molecular level. However, significant time and effort are still required to solve and complete many of these structures because of the need for manual interpretation of complex numerical data using many software packages and the repeated use of interactive three-dimensional graphics. PHENIX has been developed to provide a comprehensive system for macromolecular crystallographic structure solution with an emphasis on the automation of all procedures. This has relied on the development of algorithms that minimize or eliminate subjective input, the development of algorithms that automate procedures that are traditionally performed by hand and, finally, the development of a framework that allows a tight integration between the algorithms.
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TL;DR: A description is given of Phaser-2.1: software for phasing macromolecular crystal structures by molecular replacement and single-wavelength anomalous dispersion phasing.
Abstract: Phaser is a program for phasing macromolecular crystal structures by both molecular replacement and experimental phasing methods. The novel phasing algorithms implemented in Phaser have been developed using maximum likelihood and multivariate statistics. For molecular replacement, the new algorithms have proved to be significantly better than traditional methods in discriminating correct solutions from noise, and for single-wavelength anomalous dispersion experimental phasing, the new algorithms, which account for correlations between F+ and F−, give better phases (lower mean phase error with respect to the phases given by the refined structure) than those that use mean F and anomalous differences ΔF. One of the design concepts of Phaser was that it be capable of a high degree of automation. To this end, Phaser (written in C++) can be called directly from Python, although it can also be called using traditional CCP4 keyword-style input. Phaser is a platform for future development of improved phasing methods and their release, including source code, to the crystallographic community.
17,755 citations