scholarly journals Geometric Constraints for the Phase Problem in X-Ray Crystallography

10.29007/p2pj ◽  
2018 ◽  
Author(s):  
Corinna Heldt ◽  
Alexander Bockmayr
Keyword(s):  
Electron Density Distribution ◽  
Fourier Coefficients ◽  
Three Dimensional ◽  
Geometric Constraints ◽  
Dimensional Structure ◽  
Biological Macromolecules ◽  
Phase Problem ◽  
X Ray ◽  
X Ray Crystallography

X-ray crystallography is one of the main methods to establish the three-dimensional structure of biological macromolecules. In an X-ray experiment, one can measure only the magnitudes of the complex Fourier coefficients of the electron density distribution under study, but not their phases. The problem of recovering the lost phases is called the phase problem. Building on earlier work by Lunin/Urzhumtsev/Bockmayr, we extend their constraint-based approach to the phase problem by adding further 0-1 linear programming constraints. These constraints describe geometric properties of proteins and increase the quality of the solutions. The approach has been implemented using SCIP and CPLEX, first computational results are presented here.

Three-dimensional crystallization of membrane proteins

1988 ◽  
Vol 21 (4) ◽  
pp. 429-477 ◽  
Author(s):  
W. Kühlbrandt
Keyword(s):  
High Resolution ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Protein Complexes ◽  
Three Dimensional ◽  
Biological Macromolecules ◽  
X Ray ◽  
X Ray Crystallography ◽  
Membrane Protein Complexes ◽  
Essential Prerequisite

As recently as 10 years ago, the prospect of solving the structure of any membrane protein by X-ray crystallography seemed remote. Since then, the threedimensional (3-D) structures of two membrane protein complexes, the bacterial photosynthetic reaction centres of Rhodopseudomonas viridis (Deisenhofer et al. 1984, 1985) and of Rhodobacter sphaeroides (Allen et al. 1986, 1987 a, 6; Chang et al. 1986) have been determined at high resolution. This astonishing progress would not have been possible without the pioneering work of Michel and Garavito who first succeeded in growing 3-D crystals of the membrane proteins bacteriorhodopsin (Michel & Oesterhelt, 1980) and matrix porin (Garavito & Rosenbusch, 1980). X-ray crystallography is still the only routine method for determining the 3-D structures of biological macromolecules at high resolution and well-ordered 3-D crystals of sufficient size are the essential prerequisite.

scholarly journals Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics

2018 ◽  
Vol 19 (11) ◽  
pp. 3401 ◽  
Author(s):  
Ashutosh Srivastava ◽  
Tetsuro Nagai ◽  
Arpita Srivastava ◽  
Osamu Miyashita ◽  
Florence Tama
Keyword(s):  
Protein Dynamics ◽  
Computational Methods ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Insight Into

Protein structural biology came a long way since the determination of the first three-dimensional structure of myoglobin about six decades ago. Across this period, X-ray crystallography was the most important experimental method for gaining atomic-resolution insight into protein structures. However, as the role of dynamics gained importance in the function of proteins, the limitations of X-ray crystallography in not being able to capture dynamics came to the forefront. Computational methods proved to be immensely successful in understanding protein dynamics in solution, and they continue to improve in terms of both the scale and the types of systems that can be studied. In this review, we briefly discuss the limitations of X-ray crystallography in studying protein dynamics, and then provide an overview of different computational methods that are instrumental in understanding the dynamics of proteins and biomacromolecular complexes.

scholarly journals The Resolution in X-ray Crystallography and Single-Particle Cryogenic Electron Microscopy

Crystals ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 580
Author(s):  
Victor R.A. Dubach ◽  
Albert Guskov
Keyword(s):  
Electron Microscopy ◽  
Single Particle ◽  
Signal To Noise Ratio ◽  
Three Dimensional ◽  
Particle Analysis ◽  
Biological Macromolecules ◽  
Single Particle Analysis ◽  
X Ray ◽  
X Ray Crystallography ◽  
The Fourier Transform

X-ray crystallography and single-particle analysis cryogenic electron microscopy are essential techniques for uncovering the three-dimensional structures of biological macromolecules. Both techniques rely on the Fourier transform to calculate experimental maps. However, one of the crucial parameters, resolution, is rather broadly defined. Here, the methods to determine the resolution in X-ray crystallography and single-particle analysis are summarized. In X-ray crystallography, it is becoming increasingly more common to include reflections discarded previously by traditionally used standards, allowing for the inclusion of incomplete and anisotropic reflections into the refinement process. In general, the resolution is the smallest lattice spacing given by Bragg’s law for a particular set of X-ray diffraction intensities; however, typically the resolution is truncated by the user during the data processing based on certain parameters and later it is used during refinement. However, at which resolution to perform such a truncation is not always clear and this makes it very confusing for the novices entering the structural biology field. Furthermore, it is argued that the effective resolution should be also reported as it is a more descriptive measure accounting for anisotropy and incompleteness of the data. In single particle cryo-EM, the situation is not much better, as multiple ways exist to determine the resolution, such as Fourier shell correlation, spectral signal-to-noise ratio and the Fourier neighbor correlation. The most widely accepted is the Fourier shell correlation using a threshold of 0.143 to define the resolution (so-called “gold-standard”), although it is still debated whether this is the correct threshold. Besides, the resolution obtained from the Fourier shell correlation is an estimate of varying resolution across the density map. In reality, the interpretability of the map is more important than the numerical value of the resolution.

scholarly journals Topography Prediction of Helical Transmembrane Proteins by a New Modification of the Sliding Window Method

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maria N. Simakova ◽  
Nikolai N. Simakov
Keyword(s):  
Membrane Proteins ◽  
Transmembrane Domain ◽  
Domain Boundary ◽  
Three Dimensional ◽  
Transmembrane Proteins ◽  
Sliding Window ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Window Method

Protein functions are specified by its three-dimensional structure, which is usually obtained by X-ray crystallography. Due to difficulty of handling membrane proteins experimentally to date the structure has only been determined for a very limited part of membrane proteins (<4%). Nevertheless, investigation of structure and functions of membrane proteins is important for medicine and pharmacology and, therefore, is of significant interest. Methods of computer modeling based on the data on the primary protein structure or the symbolic amino acid sequence have become an actual alternative to the experimental method of X-ray crystallography for investigating the structure of membrane proteins. Here we presented the results of the study of 35 transmembrane proteins, mainly GPCRs, using the novel method of cascade averaging of hydrophobicity function within the limits of a sliding window. The proposed method allowed revealing 139 transmembrane domains out of 140 (or 99.3%) identified by other methods. Also 236 transmembrane domain boundary positions out of 280 (or 84%) were predicted correctly by the proposed method with deviation from the predictions made by other methods that does not exceed the detection error of this method.

scholarly journals A new on-axis multimode spectrometer for the macromolecular crystallography beamlines of the Swiss Light Source

2009 ◽  
Vol 16 (2) ◽  
pp. 173-182 ◽  
Author(s):  
Robin L. Owen ◽  
Arwen R. Pearson ◽  
Alke Meents ◽  
Pirmin Boehler ◽  
Vincent Thominet ◽  
...  
Keyword(s):  
Light Source ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Additional Information ◽  
Swiss Light Source ◽  
Induced Changes ◽  
Insight Into

X-ray crystallography at third-generation synchrotron sources permits tremendous insight into the three-dimensional structure of macromolecules. Additional information is, however, often required to aid the transition from structure to function. In situ spectroscopic methods such as UV–Vis absorption and (resonance) Raman can provide this, and can also provide a means of detecting X-ray-induced changes. Here, preliminary results are introduced from an on-axis UV–Vis absorption and Raman multimode spectrometer currently being integrated into the beamline environment at X10SA of the Swiss Light Source. The continuing development of the spectrometer is also outlined.

scholarly journals Induction of Rare Conformation of Oligosaccharide by Binding to Calcium-dependent Bacterial Lectin: X-ray Crystallography and Modelling Study

2019 ◽  
Author(s):  
Martin Lepsik ◽  
Roman Sommer ◽  
Sakonwan Kuhaudomlarp ◽  
Mickaёl Lelimousin ◽  
Emanuele Paci ◽  
...  
Keyword(s):  
Force Field ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Lewis X ◽  
X Ray ◽  
X Ray Crystallography ◽  
Calcium Dependent ◽  
Protein Receptors ◽  
Dependent Protein ◽  
Micro Organisms

ABSTRACTPathogenic micro-organisms utilize protein receptors in adhesion to host tissues, a process that in some cases relies on the interaction between lectin and human glycoconjugates. Oligosaccharide epitopes are recognized through their three-dimensional structure and their flexibility is a key issue in specificity. In this paper, we analyse by X-ray crystallography the structures of the lectin LecB from two strains of Pseudomonas aeruginosa in complex with Lewis x oligosaccharide present on cell surfaces of human tissues. An unusual conformation of the glycan was observed in all binding sites with a non-canonical syn orientation of the N-acetyl group of N-acetyl-glucosamine. A PDB-wide search revealed that such an orientation occurs only in 2% of protein/carbohydrate complexes. Theoretical chemistry calculations showed that the observed conformation is unstable in solution but stabilised by the lectin. A reliable description of LecB/Lewis x complex by force field-based methods had proven as especially challenging due to the special feature of the binding site, two closely apposed Ca2+ ions which induce strong charge delocalisation. By comparing various force-field parametrisations, we design general protocols which will be useful in near future for designing carbohydrate-based ligands (glycodrugs) against other calcium-dependent protein receptors.

scholarly journals Worldwide Protein Data Bank validation information: usage and trends

2018 ◽  
Vol 74 (3) ◽  
pp. 237-244 ◽  
Author(s):  
Oliver S. Smart ◽  
Vladimír Horský ◽  
Swanand Gore ◽  
Radka Svobodová Vařeková ◽  
Veronika Bendová ◽  
...  
Keyword(s):  
Protein Data Bank ◽  
Three Dimensional ◽  
Data Bank ◽  
Resonance Spectroscopy ◽  
X Ray ◽  
Validation Metrics ◽  
Task Forces ◽  
X Ray Crystallography ◽  
Structure Properties

Realising the importance of assessing the quality of the biomolecular structures deposited in the Protein Data Bank (PDB), the Worldwide Protein Data Bank (wwPDB) partners established Validation Task Forces to obtain advice on the methods and standards to be used to validate structures determined by X-ray crystallography, nuclear magnetic resonance spectroscopy and three-dimensional electron cryo-microscopy. The resulting wwPDB validation pipeline is an integral part of the wwPDB OneDep deposition, biocuration and validation system. The wwPDB Validation Service webserver (https://validate.wwpdb.org) can be used to perform checks prior to deposition. Here, it is shown how validation metrics can be combined to produce an overall score that allows the ranking of macromolecular structures and domains in search results. The ValTrendsDBdatabase provides users with a convenient way to access and analyse validation information and other properties of X-ray crystal structures in the PDB, including investigating trends in and correlations between different structure properties and validation metrics.

scholarly journals Reconstruction of crystal shapes by X-ray nanodiffraction from three-dimensional superlattices

2014 ◽  
Vol 47 (6) ◽  
pp. 2030-2037 ◽  
Author(s):  
Mojmír Meduňa ◽  
Claudiu V. Falub ◽  
Fabio Isa ◽  
Daniel Chrastina ◽  
Thomas Kreiliger ◽  
...  
Keyword(s):  
Structural Model ◽  
Three Dimensional ◽  
Three Dimensions ◽  
Semiconductor Layer ◽  
Dimensional Structure ◽  
Solid State Lasers ◽  
X Ray ◽  
Nondestructive Imaging ◽  
Low Dimensional

Quantitative nondestructive imaging of structural properties of semiconductor layer stacks at the nanoscale is essential for tailoring the device characteristics of many low-dimensional quantum structures, such as ultrafast transistors, solid state lasers and detectors. Here it is shown that scanning nanodiffraction of synchrotron X-ray radiation can unravel the three-dimensional structure of epitaxial crystals containing a periodic superlattice underneath their faceted surface. By mapping reciprocal space in all three dimensions, the superlattice period is determined across the various crystal facets and the very high crystalline quality of the structures is demonstrated. It is shown that the presence of the superlattice allows the reconstruction of the crystal shape without the need of any structural model.

Synopses from the poster exhibition organized by I. M. Kerr, 1. Interferon: a tertiary structure predicted from amino acid sequences

1982 ◽  
Vol 299 (1094) ◽  
pp. 125-127 ◽  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Tertiary Structure ◽  
Three Dimensional ◽  
Amino Acid Sequences ◽  
Dimensional Structure ◽  
X Ray ◽  
Three Dimensional Structure ◽  
X Ray Crystallography ◽  
Functional Studies

Functional studies on interferon would be helped by a three-dimensional structure for the molecule. However, it may be several years before the structure of the protein is determined by X-ray crystallography. We have therefore used available methods for predicting the secondary - and the tertiary - structure of a protein from its amino acid sequence to propose a tertiary model involving the packing of four a-helices. Details of this work have been published elsewhere (Sternberg & Cohen 1982).

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