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Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data

SAD phasing can be challenging when the signal-to-noise ratio is low. In such cases, having an accurate estimate of the substructure content can determine whether or not the substructure of anomalous scatterer positions can successfully be determined. Here, a likelihood-based target function is prop...

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Autores principales: Hatti, Kaushik S., McCoy, Airlie J., Read, Randy J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International Union of Crystallography 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251343/
https://www.ncbi.nlm.nih.gov/pubmed/34196615
http://dx.doi.org/10.1107/S2059798321004538
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author Hatti, Kaushik S.
McCoy, Airlie J.
Read, Randy J.
author_facet Hatti, Kaushik S.
McCoy, Airlie J.
Read, Randy J.
author_sort Hatti, Kaushik S.
collection PubMed
description SAD phasing can be challenging when the signal-to-noise ratio is low. In such cases, having an accurate estimate of the substructure content can determine whether or not the substructure of anomalous scatterer positions can successfully be determined. Here, a likelihood-based target function is proposed to accurately estimate the strength of the anomalous scattering contribution directly from the measured intensities, determining a complex correlation parameter relating the Bijvoet mates as a function of resolution. This gives a novel measure of the intrinsic anomalous signal. The SAD likelihood target function also accounts for correlated errors in the measurement of intensities from Bijvoet mates, which can arise from the effects of radiation damage. When the anomalous signal is assumed to come primarily from a substructure comprising one anomalous scatterer with a known value of f′′ and when the protein composition of the crystal is estimated correctly, the refined complex correlation parameters can be interpreted in terms of the atomic content of the primary anomalous scatterer before the substructure is known. The maximum-likelihood estimation of substructure content was tested on a curated database of 357 SAD cases with useful anomalous signal. The prior estimates of substructure content are highly correlated to the content determined by phasing calculations, with a correlation coefficient (on a log–log basis) of 0.72.
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spelling pubmed-82513432021-07-12 Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data Hatti, Kaushik S. McCoy, Airlie J. Read, Randy J. Acta Crystallogr D Struct Biol Research Papers SAD phasing can be challenging when the signal-to-noise ratio is low. In such cases, having an accurate estimate of the substructure content can determine whether or not the substructure of anomalous scatterer positions can successfully be determined. Here, a likelihood-based target function is proposed to accurately estimate the strength of the anomalous scattering contribution directly from the measured intensities, determining a complex correlation parameter relating the Bijvoet mates as a function of resolution. This gives a novel measure of the intrinsic anomalous signal. The SAD likelihood target function also accounts for correlated errors in the measurement of intensities from Bijvoet mates, which can arise from the effects of radiation damage. When the anomalous signal is assumed to come primarily from a substructure comprising one anomalous scatterer with a known value of f′′ and when the protein composition of the crystal is estimated correctly, the refined complex correlation parameters can be interpreted in terms of the atomic content of the primary anomalous scatterer before the substructure is known. The maximum-likelihood estimation of substructure content was tested on a curated database of 357 SAD cases with useful anomalous signal. The prior estimates of substructure content are highly correlated to the content determined by phasing calculations, with a correlation coefficient (on a log–log basis) of 0.72. International Union of Crystallography 2021-06-18 /pmc/articles/PMC8251343/ /pubmed/34196615 http://dx.doi.org/10.1107/S2059798321004538 Text en © Hatti, McCoy & Read 2021 https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.
spellingShingle Research Papers
Hatti, Kaushik S.
McCoy, Airlie J.
Read, Randy J.
Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
title Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
title_full Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
title_fullStr Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
title_full_unstemmed Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
title_short Likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (SAD) intensity data
title_sort likelihood-based estimation of substructure content from single-wavelength anomalous diffraction (sad) intensity data
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251343/
https://www.ncbi.nlm.nih.gov/pubmed/34196615
http://dx.doi.org/10.1107/S2059798321004538
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