scholarly journals Determination of the Structure of Biological Macromolecular Particles Using X-Ray Lasers. Achievements and Prospects

2020 ◽  
Vol 15 (2) ◽  
pp. 195-234
Author(s):  
T.E. Petrova ◽  
V.Y. Lunin
Keyword(s):  
Single Molecule ◽  
Experimental Approach ◽  
Biological Macromolecules ◽  
X Ray Diffraction ◽  
X Ray ◽  
Current State ◽  
Fundamental Possibility ◽  
Diffraction Patterns ◽  
Further Development

X-ray diffraction analysis is the main experimental approach to determining the atomic structure of biological macromolecules and their complexes. The most serious limitation of its applicability, to date, is the need to prepare a sample of the object under study in the form of a single crystal, which is caused by the extremely low intensity of rays scattered by a single molecule. The commissioning of X-ray Free-Electron Lasers with their super-powerful (by many orders of magnitude exceeding the brightness of modern synchrotrons) and ultra-short (less than 100 fs) pulse is an experimental breakthrough that allows us to expect to obtain diffraction patterns from individual biological particles and then determine their structure. The first experimental results demonstrate the fundamental possibility of such an approach and are accompanied by the publication of a significant number of articles on various aspects of the development of the method. The purpose of this article is to discuss the current state of art in this area, evaluate the results achieved and discuss the prospects for further development of the method based on the analysis of publications in the world scientific literature of recent years and the experience of work carried out by the review authors and their colleagues.

scholarly journals Born out of Fire and Ice: Polymorph Studies of the Antiviral Famciclovir

Crystals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 129
Author(s):  
Liana Vella-Zarb ◽  
Ulrich Baisch
Keyword(s):  
Variable Temperature ◽  
Chemical Properties ◽  
Crystal Form ◽  
X Ray Diffraction ◽  
Crystal Forms ◽  
X Ray ◽  
Physical Chemical ◽  
Diffraction Patterns ◽  
Crystalline Forms

There is much interest and focus on solid forms of famciclovir. However, in spite of the abundance of reported differences in oral bioavailability, compressibility, and other physical–chemical properties of the various crystal forms of this drug, very little precise structural analysis is available in the literature to date. The form used in the commercial formulation is the anhydrous form I. Patents and patent applications report three different anhydrous crystalline forms on the basis of unindexed powder diffraction patterns. Single-crystal and variable-temperature X-ray diffraction experiments using the commercially available anhydrous form of famciclovir were carried out and led not only to the crystal structure determination of the anhydrous form I, but also to discovery of a new crystal form of anhydrous famciclovir from powder data.

scholarly journals Synthesis of the Modifications of Ca2SiO4 and the Determination of their Powder X-ray Diffraction Patterns

1963 ◽  
Vol 71 (806) ◽  
pp. 63-68 ◽  
Author(s):  
Goro YAMAGUCHI ◽  
Yoshio ONO ◽  
Shigeo KAWAMURA ◽  
Yoshiaki SODA
Keyword(s):  
X Ray Diffraction ◽  
X Ray ◽  
Diffraction Patterns

scholarly journals X-Ray Diffraction from Magnetically Oriented Microcrystal Suspension

2014 ◽  
Vol 70 (a1) ◽  
pp. C1136-C1136
Author(s):  
Kazuaki Aburaya ◽  
Chiaki Tsuboi ◽  
Fumiko Kimura ◽  
Kenji Matsumoto ◽  
Masataka Maeyama ◽  
...  
Keyword(s):  
Single Crystal ◽  
Magnetic Circuit ◽  
X Ray Diffraction ◽  
Glass Capillary ◽  
Uv Curable ◽  
X Ray ◽  
Novel Method ◽  
Diffraction Patterns ◽  
Magnetic Field Generator

A three dimensionally magnetically oriented microcrystal array (3D-MOMA) is attractive to determination of a crystal structure as well as a molecular structure because it does not require a single crystal with sufficient size and quality for diffraction studies. We have developed a novel method to fabricate 3D-MOMA and determined several crystal structures using the 3D-MOMAs[1],[2]. However, the structure determination through MOMA requires a solidification treatment with UV curable monomer prior to X-ray diffraction experiment. We have developed a new X-ray diffractometer equipped with a magnetic field generator, which makes it possible to collect diffraction data without the solidification treatment. In this poster, we describe X-ray diffraction analyses of a magnetically oriented microcrystal suspension (MOMS) of L-alanine without the solidification treatment. A suspension of L-alanine microcrystals was poured in a glass capillary and rotated at a constant speed in a magnetic circuit attached in the X-ray diffractometer. Then, diffraction images were collected every 60 seconds. In the initial phase, the diffraction pattern showed a broad shape similar to that from a powder sample. As time goes on, diffraction patterns have gradually changed to single-crystal like patterns. After 2 hours, the shape of diffraction spots became as sharp as that of a single crystal. This observation shows that the microcrystals are oriented in the same direction. Owing to the improvement of the magnetic circuit and X-ray diffractometer, the quality of the diffraction has been greatly improved compared to that reported previously[3]. Further details of the analyses will be shown in the poster.

Kinematics Meets Crystallography: The Concept of a Motion Space

2014 ◽  
Author(s):  
Gregory S. Chirikjian
Keyword(s):  
Rigid Body ◽  
Molecular Structures ◽  
New Drugs ◽  
Dimensional Structure ◽  
Biological Macromolecules ◽  
Molecular Replacement ◽  
X Ray Diffraction ◽  
X Ray ◽  
Rigid Body Motions ◽  
Diffraction Patterns

In this paper, it is shown how rigid-body kinematics can be used to assist in determining the atomic structure of proteins and nucleic acids when using x-ray crystallography, which is a powerful method for structure determination. The importance of determining molecular structures for understanding biological processes and for the design of new drugs is well known. Phasing is a necessary step in determining the three-dimensional structure of molecules from x-ray diffraction patterns. A computational approach called molecular replacement (MR) is a well-established method for phasing of x-ray diffraction patterns for crystals composed of biological macromolecules. In MR, a search is performed over positions and orientations of a known biomolecular structure within a model of the crystallographic asymmetric unit, or, equivalently, multiple symmetry-related molecules in the crystallographic unit cell. Unlike the discrete space groups known to crystallographers and the continuous rigid-body motions known to kinematicians, the set of motions over which molecular replacement searches are performed does not form a group. Rather, it is a coset space of the group of continuous rigid-body motions, SE(3), with respect to the crystallographic space group of the crystal, which is a discrete sub-group of SE(3). Properties of these ‘motion spaces’ (which are compact manifolds) are investigated here.

Structure determination of forms I and II of phenobarbital from X-ray powder diffraction

2005 ◽  
Vol 61 (1) ◽  
pp. 80-88 ◽  
Author(s):  
Cyril Platteau ◽  
Jacques Lefebvre ◽  
Stephanie Hemon ◽  
Carsten Baehtz ◽  
Florence Danede ◽  
...  
Keyword(s):  
X Ray Diffraction ◽  
Rietveld Refinements ◽  
Space Group ◽  
X Ray ◽  
Bragg Peak Profiles ◽  
Monte Carlo Simulated Annealing ◽  
Crystal Structural ◽  
Diffraction Patterns ◽  
Annealing Method

From pure powders of forms I and II of phenobarbital, X-ray diffraction patterns were recorded at room temperature. The starting crystal structural models were found by a Monte-Carlo simulated annealing method. The structures of the two forms were obtained through Rietveld refinements. Soft restraints were applied on bond lengths and bond angles, all H-atom positions were calculated. The cell of form I is monoclinic with the space group P21/n, Z = 12, Z′ = 3. Form II has a triclinic cell, with the space group P\bar 1, Z = 6, Z′ = 3. For both forms, the crystal cohesion is achieved by networks of N—H...O hydrogen bonds along [101]. The broadening of the Bragg peak profiles is interpreted in terms of isotropic strain effects and anisotropic size effects.

Sign in / Sign up

Export Citation Format

Share Document