Lipid Bilayer Structure Refinement with SAXS/SANS Based Restrained Ensemble Molecular Dynamics

10.26434/chemrxiv.14182763.v2 ◽

2021 ◽

Author(s):

Yevhen Cherniavskyi ◽

Svetlana Baoukina ◽

Bryan W. Holland ◽

D. Peter Tieleman

Keyword(s):

Molecular Dynamics ◽

Lipid Bilayers ◽

Small Angle ◽

Structure Refinement ◽

Small Angle Scattering ◽

Scattering Data ◽

Bilayer Structure ◽

Lipid Molecule ◽

Scattering Intensity ◽

Angle Scattering

Small-angle scattering is a powerful technique that can probe the structure of lipid bilayers on the nanometer scale. Retrieving the real space structure of lipid bilayers from the scattering intensity can be a challenging task, as their fluid nature results in a liquid-like scattering pattern which is hard to interpret. The standard approach to this problem is to describe the bilayer structure as a sum of density distributions of separate components of the lipid molecule and then to fit the parameters of the distributions against experimental data. The accuracy of the density-based analysis is partially limited by the choice of the functions used to describe component distributions, especially in the case of multi-component bilayers. The number of parameters in the model is balanced by the need for an accurate description of the underlying bilayer structure and the risk of overfitting the data. Here, we present an alternative method for the interpretation of small-angle scattering intensity data for lipid bilayers. The method is based on restrained ensemble molecular dynamics simulations that allow direct incorporation of the scattering data into the simulations in the form of a restraining potential. This approach combines the information implicitly contained in the simulation force field with structural data from the scattering intensity and is free from prior assumptions regarding the bilayer structure.<br>

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Lipid Bilayer Structure Refinement with SAXS/SANS Based Restrained Ensemble Molecular Dynamics

10.26434/chemrxiv.14182763 ◽

2021 ◽

Author(s):

Yevhen Cherniavskyi ◽

Svetlana Baoukina ◽

Bryan W. Holland ◽

D. Peter Tieleman

Keyword(s):

Molecular Dynamics ◽

Lipid Bilayers ◽

Small Angle ◽

Structure Refinement ◽

Small Angle Scattering ◽

Scattering Data ◽

Bilayer Structure ◽

Lipid Molecule ◽

Scattering Intensity ◽

Angle Scattering

Small-angle scattering is a powerful technique that can probe the structure of lipid bilayers on the nanometer scale. Retrieving the real space structure of lipid bilayers from the scattering intensity can be a challenging task, as their fluid nature results in a liquid-like scattering pattern which is hard to interpret. The standard approach to this problem is to describe the bilayer structure as a sum of density distributions of separate components of the lipid molecule and then to fit the parameters of the distributions against experimental data. The accuracy of the density-based analysis is partially limited by the choice of the functions used to describe component distributions, especially in the case of multi-component bilayers. The number of parameters in the model is balanced by the need for an accurate description of the underlying bilayer structure and the risk of overfitting the data. Here, we present an alternative method for the interpretation of small-angle scattering intensity data for lipid bilayers. The method is based on restrained ensemble molecular dynamics simulations that allow direct incorporation of the scattering data into the simulations in the form of a restraining potential. This approach combines the information implicitly contained in the simulation force field with structural data from the scattering intensity and is free from prior assumptions regarding the bilayer structure.<br>

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Rapid and accurate calculation of small-angle scattering profiles using the golden ratio

Journal of Applied Crystallography ◽

10.1107/s002188981301666x ◽

2013 ◽

Vol 46 (4) ◽

pp. 1171-1177 ◽

Cited By ~ 25

Author(s):

Max C. Watson ◽

Joseph E. Curtis

Keyword(s):

Small Angle ◽

Golden Ratio ◽

Expansion Method ◽

Multipole Expansion ◽

Small Angle Scattering ◽

Scattering Data ◽

Approximation Technique ◽

Scattering Intensity ◽

Angle Scattering ◽

Multipole Expansion Method

Calculating the scattering intensity of anN-atom system is a numerically exhaustingO(N2) task. A simple approximation technique that scales linearly with the number of atoms is presented. Using an exact expression for the scattering intensityI(q) at a given wavevectorq, the rotationally averaged intensityI(q) is computed by evaluatingI(q) in several scattering directions. The orientations of theqvectors are taken from a quasi-uniform spherical grid generated by the golden ratio. Using various biomolecules as examples, this technique is compared with an established multipole expansion method. For a given level of speed, the technique is more accurate than the multipole expansion for anisotropically shaped molecules, while comparable in accuracy for globular shapes. The processing time scales sub-linearly inNwhen the atoms are identical and lie on a lattice. The procedure is easily implemented and should accelerate the analysis of small-angle scattering data.

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Full structural ensembles of intrinsically disordered proteins from unbiased molecular dynamics simulations

Communications Biology ◽

10.1038/s42003-021-01759-1 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Utsab R. Shrestha ◽

Jeremy C. Smith ◽

Loukas Petridis

Keyword(s):

Molecular Dynamics ◽

Small Angle ◽

Intrinsically Disordered Proteins ◽

Chemical Shifts ◽

Small Angle Scattering ◽

Disordered Proteins ◽

Scattering Data ◽

General Applicability ◽

Intrinsically Disordered ◽

Angle Scattering

AbstractMolecular dynamics (MD) simulation is widely used to complement ensemble-averaged experiments of intrinsically disordered proteins (IDPs). However, MD often suffers from limitations of inaccuracy. Here, we show that enhancing the sampling using Hamiltonian replica-exchange MD (HREMD) led to unbiased and accurate ensembles, reproducing small-angle scattering and NMR chemical shift experiments, for three IDPs of varying sequence properties using two recently optimized force fields, indicating the general applicability of HREMD for IDPs. We further demonstrate that, unlike HREMD, standard MD can reproduce experimental NMR chemical shifts, but not small-angle scattering data, suggesting chemical shifts are insufficient for testing the validity of IDP ensembles. Surprisingly, we reveal that despite differences in their sequence, the inter-chain statistics of all three IDPs are similar for short contour lengths (< 10 residues). The results suggest that the major hurdle of generating an accurate unbiased ensemble for IDPs has now been largely overcome.

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Vesicle Viewer: Online Analysis of Small Angle Scattering from Lipid Vesicles

10.26434/chemrxiv.14454645 ◽

2021 ◽

Author(s):

Aislyn Lewis-Laurent ◽

Milka Doktorova ◽

Frederick A. Heberle ◽

Drew Marquardt

Keyword(s):

Lipid Bilayers ◽

Small Angle ◽

Web Applications ◽

Structural Parameters ◽

Lipid Vesicles ◽

Small Angle Scattering ◽

Scattering Data ◽

Web Based ◽

Angle Scattering ◽

Area Per Lipid

In this project, we developed an internet-based application, called Vesicle Viewer, to visualize and analyze small angle scattering data generated in the study of lipid bilayers. Vesicle Viewer models SAS data using the EZ-SDP model. In this way, key bilayer structural parameters, such as area per lipid and bilayer thickness, can be easily determined. This application primarily uses Django, a python package specialized for the development of robust web applications. In addition, several other libraries are used to support the more technical aspects of the project – notable examples are MatPlotLib (for graphs) and NumPy (for calculations). Without the barrier of downloading and installing software, the development of this web-based application will allow scientists all over the world to take advantage of this solution, regardless of their preferred operating system.

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Vesicle Viewer: Online Analysis of Small Angle Scattering from Lipid Vesicles

10.26434/chemrxiv.14454645.v1 ◽

2021 ◽

Author(s):

Aislyn Lewis-Laurent ◽

Milka Doktorova ◽

Frederick A. Heberle ◽

Drew Marquardt

Keyword(s):

Lipid Bilayers ◽

Small Angle ◽

Web Applications ◽

Structural Parameters ◽

Lipid Vesicles ◽

Small Angle Scattering ◽

Scattering Data ◽

Web Based ◽

Angle Scattering ◽

Area Per Lipid

In this project, we developed an internet-based application, called Vesicle Viewer, to visualize and analyze small angle scattering data generated in the study of lipid bilayers. Vesicle Viewer models SAS data using the EZ-SDP model. In this way, key bilayer structural parameters, such as area per lipid and bilayer thickness, can be easily determined. This application primarily uses Django, a python package specialized for the development of robust web applications. In addition, several other libraries are used to support the more technical aspects of the project – notable examples are MatPlotLib (for graphs) and NumPy (for calculations). Without the barrier of downloading and installing software, the development of this web-based application will allow scientists all over the world to take advantage of this solution, regardless of their preferred operating system.

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HierarchicalO(N) computation of small-angle scattering profiles and their associated derivatives

Journal of Applied Crystallography ◽

10.1107/s1600576714004671 ◽

2014 ◽

Vol 47 (2) ◽

pp. 755-761 ◽

Cited By ~ 4

Author(s):

Konstantin Berlin ◽

Nail A. Gumerov ◽

David Fushman ◽

Ramani Duraiswami

Keyword(s):

Small Angle ◽

Structure Refinement ◽

Optimization Procedure ◽

Small Angle Scattering ◽

Scattering Data ◽

X Ray Scattering ◽

Macromolecular Systems ◽

Angle Scattering ◽

Gradient Based ◽

Speed Up

The need for fast approximate algorithms for Debye summation arises in computations performed in crystallography, small/wide-angle X-ray scattering and small-angle neutron scattering. When integrated into structure refinement protocols these algorithms can provide significant speed up over direct all-atom-to-all-atom computation. However, these protocols often employ an iterative gradient-based optimization procedure, which then requires derivatives of the profile with respect to atomic coordinates. This article presents an accurate,O(N) cost algorithm for the computation of scattering profile derivatives. The results reported here show orders of magnitude improvement in computational efficiency, while maintaining the prescribed accuracy. This opens the possibility to efficiently integrate small-angle scattering data into the structure determination and refinement of macromolecular systems.

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2017 publication guidelines for structural modelling of small-angle scattering data from biomolecules in solution: an update

Acta Crystallographica Section D Structural Biology ◽

10.1107/s2059798317011597 ◽

2017 ◽

Vol 73 (9) ◽

pp. 710-728 ◽

Cited By ~ 107

Author(s):

Jill Trewhella ◽

Anthony P. Duff ◽

Dominique Durand ◽

Frank Gabel ◽

J. Mitchell Guss ◽

...

Keyword(s):

Small Angle ◽

Task Force ◽

Data Bank ◽

Small Angle Scattering ◽

Scattering Data ◽

Quality Data ◽

Angle Scattering ◽

Publication Guidelines ◽

Guidelines And Recommendations

In 2012, preliminary guidelines were published addressing sample quality, data acquisition and reduction, presentation of scattering data and validation, and modelling for biomolecular small-angle scattering (SAS) experiments. Biomolecular SAS has since continued to grow and authors have increasingly adopted the preliminary guidelines. In parallel, integrative/hybrid determination of biomolecular structures is a rapidly growing field that is expanding the scope of structural biology. For SAS to contribute maximally to this field, it is essential to ensure open access to the information required for evaluation of the quality of SAS samples and data, as well as the validity of SAS-based structural models. To this end, the preliminary guidelines for data presentation in a publication are reviewed and updated, and the deposition of data and associated models in a public archive is recommended. These guidelines and recommendations have been prepared in consultation with the members of the International Union of Crystallography (IUCr) Small-Angle Scattering and Journals Commissions, the Worldwide Protein Data Bank (wwPDB) Small-Angle Scattering Validation Task Force and additional experts in the field.

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