Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.

Anomalous small angle X-ray scattering can in principle be used to determine distances between metal label species on biological molecules. Previous experimental studies in the past were unable to distinguish the label-label scattering contribution from that of the molecule, because of the use of at...

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Main Authors: Pinfield, Valerie J., Scott, David J.
Format: Article
Published: Public Library of Science 2014
Online Access:https://eprints.nottingham.ac.uk/41971/
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author Pinfield, Valerie J.
Scott, David J.
author_facet Pinfield, Valerie J.
Scott, David J.
author_sort Pinfield, Valerie J.
building Nottingham Research Data Repository
collection Online Access
description Anomalous small angle X-ray scattering can in principle be used to determine distances between metal label species on biological molecules. Previous experimental studies in the past were unable to distinguish the label-label scattering contribution from that of the molecule, because of the use of atomic labels; these labels contribute only a small proportion of the total scattering signal. However, with the development of nanocrystal labels (of 50-100 atoms) there is the possibility for a renewed attempt at applying anomalous small angle X-ray scattering for distance measurement. This is because the contribution to the scattered signal is necessarily considerably stronger than for atomic labels. Here we demonstrate through simulations, the feasibility of the technique to determine the end-to-end distances of labelled nucleic acid molecules as well as other internal distances mimicking a labelled DNA binding protein if the labels are dissimilar metal nanocrystals. Of crucial importance is the ratio of mass of the nanocrystals to that of the labelled macromolecule, as well as the level of statistical errors in the scattering intensity measurements. The mathematics behind the distance determination process is presented, along with a fitting routine than incorporates maximum entropy regularisation.
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spelling nottingham-419712020-05-04T16:46:23Z https://eprints.nottingham.ac.uk/41971/ Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution. Pinfield, Valerie J. Scott, David J. Anomalous small angle X-ray scattering can in principle be used to determine distances between metal label species on biological molecules. Previous experimental studies in the past were unable to distinguish the label-label scattering contribution from that of the molecule, because of the use of atomic labels; these labels contribute only a small proportion of the total scattering signal. However, with the development of nanocrystal labels (of 50-100 atoms) there is the possibility for a renewed attempt at applying anomalous small angle X-ray scattering for distance measurement. This is because the contribution to the scattered signal is necessarily considerably stronger than for atomic labels. Here we demonstrate through simulations, the feasibility of the technique to determine the end-to-end distances of labelled nucleic acid molecules as well as other internal distances mimicking a labelled DNA binding protein if the labels are dissimilar metal nanocrystals. Of crucial importance is the ratio of mass of the nanocrystals to that of the labelled macromolecule, as well as the level of statistical errors in the scattering intensity measurements. The mathematics behind the distance determination process is presented, along with a fitting routine than incorporates maximum entropy regularisation. Public Library of Science 2014-04-23 Article PeerReviewed Pinfield, Valerie J. and Scott, David J. (2014) Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution. PloS ONE, 9 (4). e95664/1-e95664/14. ISSN 1932-6203 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0095664 doi:10.1371/journal.pone.0095664 doi:10.1371/journal.pone.0095664
spellingShingle Pinfield, Valerie J.
Scott, David J.
Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.
title Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.
title_full Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.
title_fullStr Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.
title_full_unstemmed Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.
title_short Anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.
title_sort anomalous small angle x-ray scattering simulations: proof of concept for distance measurements for nanoparticle-labelled biomacromolecules in solution.
url https://eprints.nottingham.ac.uk/41971/
https://eprints.nottingham.ac.uk/41971/
https://eprints.nottingham.ac.uk/41971/