scholarly journals Obtaining tertiary protein structures by the ab-initio interpretation of small angle X-ray scattering data

2019 ◽  
Author(s):  
Christopher Prior ◽  
Owen R Davies ◽  
Daniel Bruce ◽  
Ehmke Pohl
Keyword(s):  
Ab Initio ◽  
Small Angle ◽  
Protein Structures ◽  
Scattering Data ◽  
Ab Initio Method ◽  
Primary Sequence ◽  
Saxs Data ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

ABSTRACTSmall angle X-ray scattering (SAXS) has become an important tool to investigate the structure of proteins in solution. In this paper we present a novel ab-initio method to represent polypeptide chains as discrete curves that can be used to derive a meaningful three-dimensional model from only the primary sequence and experimental SAXS data. High resolution crystal structures were used to generate probability density functions for each of the common secondary structural elements found in proteins. These are used to place realistic restraints on the model curve’s geometry. To evaluate the quality of potential models and demonstrate the efficacy of this novel technique we developed a new statistic to compare the entangled geometry of two open curves, based on mathematical techniques from knot theory. The chain model is coupled with a novel explicit hydration shell model in order derive physically meaningful 3D models by optimizing configurations against experimental SAXS data using a monte-caro based algorithm. We show that the combination of our ab-initio method with spatial restraints based on contact predictions successfully derives a biologically plausible model of the coiled–coil component of the human synaptonemal complex central element protein.SIGNIFICANCESmall-angle X-ray scattering allows for structure determination of biological macromolecules and their complexes in aqueous solution. Using a discrete curve representation of the polypeptide chain and combining it with empirically determined constraints and a realistic solvent model we are now able to derive realistic ab-initio 3-dimensional models from BioSAXS data. The method only require a primary sequence and the scattering data form the user.

scholarly journals Obtaining Tertiary Protein Structures by the ab Initio Interpretation of Small Angle X-ray Scattering Data

2020 ◽  
Vol 16 (3) ◽  
pp. 1985-2001 ◽  
Author(s):  
Christopher Prior ◽  
Owen R. Davies ◽  
Daniel Bruce ◽  
Ehmke Pohl
Keyword(s):  
Ab Initio ◽  
Small Angle ◽  
Protein Structures ◽  
Scattering Data ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

Structural refinement by restrained molecular-dynamics algorithm with small-angle X-ray scattering constraints for a biomolecule

2004 ◽  
Vol 37 (1) ◽  
pp. 103-109 ◽  
Author(s):  
Masaki Kojima ◽  
Alexander A. Timchenko ◽  
Junichi Higo ◽  
Kazuki Ito ◽  
Hiroshi Kihara ◽  
...  
Keyword(s):  
Crystal Structure ◽  
Molecular Dynamics ◽  
Small Angle ◽  
Protein Structures ◽  
Saxs Data ◽  
X Ray ◽  
X Ray Scattering ◽  
Saxs Curve ◽  
Restrained Molecular Dynamics ◽  
Ray Scattering

A new algorithm to refine protein structures in solution from small-angle X-ray scattering (SAXS) data was developed based on restrained molecular dynamics (MD). In the method, the sum of squared differences between calculated and observed SAXS intensities was used as a constraint energy function, and the calculation was started from given atomic coordinates, such as those of the crystal. In order to reduce the contribution of the hydration effect to the deviation from the experimental (objective) curve during the dynamics, and purely as an estimate of the efficiency of the algorithm, the calculation was first performed assuming the SAXS curve corresponding to the crystal structure as the objective curve. Next, the calculation was carried out with `real' experimental data, which yielded a structure that satisfied the experimental SAXS curve well. The SAXS data for ribonuclease T1, a single-chain globular protein, were used for the calculation, along with its crystal structure. The results showed that the present algorithm was very effective in the refinement and adjustment of the initial structure so that it could satisfy the objective SAXS data.

scholarly journals Guinier peak analysis for visual and automated inspection of small-angle X-ray scattering data

2016 ◽  
Vol 49 (5) ◽  
pp. 1412-1419 ◽  
Author(s):  
Christopher D. Putnam
Keyword(s):  
Small Angle ◽  
Peak Position ◽  
Scattering Data ◽  
Radius Of Gyration ◽  
Automated Inspection ◽  
Elongation Ratio ◽  
Saxs Data ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

The Guinier region in small-angle X-ray scattering (SAXS) defines the radius of gyration,Rg, and the forward scattering intensity,I(0). In Guinier peak analysis (GPA), the plot ofqI(q)versus q2transforms the Guinier region into a characteristic peak for visual and automated inspection of data. Deviations of the peak position from the theoretical position in dimensionless GPA plots can suggest parameter errors, problematic low-resolution data, some kinds of intermolecular interactions or elongated scatters. To facilitate automated analysis by GPA, the elongation ratio (ER), which is the ratio of the areas in the pair-distribution functionP(r) after and before theP(r) maximum, was characterized; symmetric samples have ER values around 1, and samples with ER values greater than 5 tend to be outliers in GPA analysis. Use of GPA+ER can be a helpful addition to SAXS data analysis pipelines.

scholarly journals A customizable software for fast reduction and analysis of large X-ray scattering data sets: applications of the newDPDAKpackage to small-angle X-ray scattering and grazing-incidence small-angle X-ray scattering

2014 ◽  
Vol 47 (5) ◽  
pp. 1797-1803 ◽  
Author(s):  
Gunthard Benecke ◽  
Wolfgang Wagermaier ◽  
Chenghao Li ◽  
Matthias Schwartzkopf ◽  
Gero Flucke ◽  
...  
Keyword(s):  
Small Angle ◽  
Data Reduction ◽  
Grazing Incidence ◽  
Scattering Data ◽  
Limiting Factor ◽  
Online Data ◽  
Saxs Data ◽  
X Ray ◽  
X Ray Scattering ◽  
Ray Scattering

X-ray scattering experiments at synchrotron sources are characterized by large and constantly increasing amounts of data. The great number of files generated during a synchrotron experiment is often a limiting factor in the analysis of the data, since appropriate software is rarely available to perform fast and tailored data processing. Furthermore, it is often necessary to perform online data reduction and analysis during the experiment in order to interactively optimize experimental design. This article presents an open-source software package developed to process large amounts of data from synchrotron scattering experiments. These data reduction processes involve calibration and correction of raw data, one- or two-dimensional integration, as well as fitting and further analysis of the data, including the extraction of certain parameters. The software,DPDAK(directly programmable data analysis kit), is based on a plug-in structure and allows individual extension in accordance with the requirements of the user. The article demonstrates the use ofDPDAKfor on- and offline analysis of scanning small-angle X-ray scattering (SAXS) data on biological samples and microfluidic systems, as well as for a comprehensive analysis of grazing-incidence SAXS data. In addition to a comparison with existing software packages, the structure ofDPDAKand the possibilities and limitations are discussed.

scholarly journals SAXSDom: Modeling multi-domain protein structures using small-angle X-ray scattering data

2019 ◽  
Author(s):  
Jie Hou ◽  
Badri Adhikari ◽  
John J. Tanner ◽  
Jianlin Cheng
Keyword(s):  
Homology Modeling ◽  
Small Angle ◽  
Tertiary Structure ◽  
Protein Structures ◽  
Scattering Data ◽  
Multidomain Proteins ◽  
X Ray ◽  
X Ray Scattering ◽  
Domain Protein ◽  
Ray Scattering

AbstractMany proteins are composed of several domains that pack together into a complex tertiary structure. Some multidomain proteins can be challenging for protein structure modeling, particularly those for which templates can be found for the domains but not for the entire sequence. In such cases, homology modeling can generate high quality models of the domains but not for the assembled protein. Small-angle X-ray scattering (SAXS) reports on the solution structural properties of proteins and has the potential for guiding homology modeling of multidomain proteins. In this work, we describe a novel multi-domain protein assembly modeling method, SAXSDom, that integrates experimental knowledge from SAXS profiles with probabilistic Input-Output Hidden Markov model (IOHMM). Four scoring functions to account for the energetic contribution of SAXS restraints for domain assembly were developed and tested. The method was evaluated on multi-domain proteins from two public datasets. Based on the results, the accuracy of domain assembly was improved for 40 out of 46 CASP multi-domain proteins in terms of RMSD and TM-score when SAXS information was used. Our method also achieved higher accuracy for at least 45 out of 73 multi-domain proteins according to RMSD and TM-score metrics in the AIDA dataset. The results demonstrate that SAXS data can provide useful information to improve the accuracy of domain-domain assembly. The source code and tool packages are available at http://github.com/multicom-toolbox/SAXSDom.

scholarly journals The accurate assessment of small-angle X-ray scattering data

2015 ◽  
Vol 71 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Thomas D. Grant ◽  
Joseph R. Luft ◽  
Lester G. Carter ◽  
Tsutomu Matsui ◽  
Thomas M. Weiss ◽  
...  
Keyword(s):  
Data Quality ◽  
Small Angle ◽  
Small Sample ◽  
Quality Analysis ◽  
Scattering Data ◽  
Saxs Data ◽  
X Ray ◽  
X Ray Scattering ◽  
Data Quality Metrics ◽  
Ray Scattering

Small-angle X-ray scattering (SAXS) has grown in popularity in recent times with the advent of bright synchrotron X-ray sources, powerful computational resources and algorithms enabling the calculation of increasingly complex models. However, the lack of standardized data-quality metrics presents difficulties for the growing user community in accurately assessing the quality of experimental SAXS data. Here, a series of metrics to quantitatively describe SAXS data in an objective manner using statistical evaluations are defined. These metrics are applied to identify the effects of radiation damage, concentration dependence and interparticle interactions on SAXS data from a set of 27 previously described targets for which high-resolution structures have been determinedviaX-ray crystallography or nuclear magnetic resonance (NMR) spectroscopy. The studies show that these metrics are sufficient to characterize SAXS data quality on a small sample set with statistical rigor and sensitivity similar to or better than manual analysis. The development of data-quality analysis strategies such as these initial efforts is needed to enable the accurate and unbiased assessment of SAXS data quality.

scholarly journals Biasing RNA coarse-grained folding simulations with Small--Angle X--ray Scattering (SAXS) data

2021 ◽  
Author(s):  
Liuba Mazzanti ◽  
Lina Alferkh ◽  
Elisa Frezza ◽  
Samuela Pasquali
Keyword(s):  
High Resolution ◽  
Small Angle ◽  
Conformational Space ◽  
Coarse Grained ◽  
Scattering Data ◽  
Saxs Data ◽  
X Ray ◽  
Rna Molecules ◽  
X Ray Scattering ◽  
Ray Scattering

RNA molecules can easily adopt alternative structures in response to different environmental conditions. As a result, a molecule's energy landscape is rough and can exhibits a multitude of deep basins. In the absence of a high-resolution structure, Small Angle X-ray Scattering data (SAXS) can narrow down the conformational space available to the molecule and be used in conjunction with physical modeling to obtain high-resolution putative structures to be further tested by experiments. Because of the low-resolution of this data, it is natural to implement the integration of SAXS data into simulations using a coarse-grained representation of the molecule, allowing for much wider searches and faster evaluation of SAXS theoretical intensity curves than with atomistic models. We present here the theoretical framework and the implementation of a simulation approach based on our coarse-grained model HiRE-RNA combined with SAXS evaluations "on-the-fly" leading the simulation toward conformations agreeing with the scattering data, starting from partially folded structures as the ones that can easily be obtained from secondary structures predictions based tools. We show on three benchmark systems how our approach can successfully achieve high-resolution structures with remarkable similarity with the native structure recovering not only the overall shape, as imposed by SAXS data, but also the details of initially missing base pairs.

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