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Title: Improving experimental phases for strong reflections prior to density modification

Abstract

Experimental phasing of diffraction data from macromolecular crystals involves deriving phase probability distributions. These distributions are often bimodal, making their weighted average, the centroid phase, improbable, so that electron-density maps computed using centroid phases are often non-interpretable. Density modification brings in information about the characteristics of electron density in protein crystals. In successful cases, this allows a choice between the modes in the phase probability distributions, and the maps can cross the borderline between non-interpretable and interpretable. Based on the suggestions by Vekhter [Vekhter (2005), Acta Cryst. D61, 899–902], the impact of identifying optimized phases for a small number of strong reflections prior to the density-modification process was investigated while using the centroid phase as a starting point for the remaining reflections. A genetic algorithm was developed that optimizes the quality of such phases using the skewness of the density map as a target function. Phases optimized in this way are then used in density modification. In most of the tests, the resulting maps were of higher quality than maps generated from the original centroid phases. In one of the test cases, the new method sufficiently improved a marginal set of experimental SAD phases to enable successful map interpretation. Lastly,more » a computer program,SISA, has been developed to apply this method for phase improvement in macromolecular crystallography.« less

Authors:
 [1];  [2];  [3];  [4]
  1. Univ. of Lubeck, Lubeck (Germany)
  2. Univ. of Lubeck, Lubeck (Germany); Chinese Academy of Sciences, Shanghai (People's Republic of China)
  3. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
  4. Univ. of Cambridge, Cambridge (England)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1255151
Report Number(s):
LA-UR-15-29209
Journal ID: ISSN 0907-4449; ABCRE6; PII: S0907444913018167
Grant/Contract Number:  
AC52-06NA25396
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Acta Crystallographica. Section D: Biological Crystallography
Additional Journal Information:
Journal Volume: 69; Journal Issue: 10; Journal ID: ISSN 0907-4449
Publisher:
International Union of Crystallography
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; experimental phasing; density modification; genetic algorithms

Citation Formats

Uervirojnangkoorn, Monarin, Hilgenfeld, Rolf, Terwilliger, Thomas C., and Read, Randy J. Improving experimental phases for strong reflections prior to density modification. United States: N. p., 2013. Web. doi:10.1107/S0907444913018167.
Uervirojnangkoorn, Monarin, Hilgenfeld, Rolf, Terwilliger, Thomas C., & Read, Randy J. Improving experimental phases for strong reflections prior to density modification. United States. https://doi.org/10.1107/S0907444913018167
Uervirojnangkoorn, Monarin, Hilgenfeld, Rolf, Terwilliger, Thomas C., and Read, Randy J. 2013. "Improving experimental phases for strong reflections prior to density modification". United States. https://doi.org/10.1107/S0907444913018167. https://www.osti.gov/servlets/purl/1255151.
@article{osti_1255151,
title = {Improving experimental phases for strong reflections prior to density modification},
author = {Uervirojnangkoorn, Monarin and Hilgenfeld, Rolf and Terwilliger, Thomas C. and Read, Randy J.},
abstractNote = {Experimental phasing of diffraction data from macromolecular crystals involves deriving phase probability distributions. These distributions are often bimodal, making their weighted average, the centroid phase, improbable, so that electron-density maps computed using centroid phases are often non-interpretable. Density modification brings in information about the characteristics of electron density in protein crystals. In successful cases, this allows a choice between the modes in the phase probability distributions, and the maps can cross the borderline between non-interpretable and interpretable. Based on the suggestions by Vekhter [Vekhter (2005), Acta Cryst. D61, 899–902], the impact of identifying optimized phases for a small number of strong reflections prior to the density-modification process was investigated while using the centroid phase as a starting point for the remaining reflections. A genetic algorithm was developed that optimizes the quality of such phases using the skewness of the density map as a target function. Phases optimized in this way are then used in density modification. In most of the tests, the resulting maps were of higher quality than maps generated from the original centroid phases. In one of the test cases, the new method sufficiently improved a marginal set of experimental SAD phases to enable successful map interpretation. Lastly, a computer program,SISA, has been developed to apply this method for phase improvement in macromolecular crystallography.},
doi = {10.1107/S0907444913018167},
url = {https://www.osti.gov/biblio/1255151}, journal = {Acta Crystallographica. Section D: Biological Crystallography},
issn = {0907-4449},
number = 10,
volume = 69,
place = {United States},
year = {Fri Sep 20 00:00:00 EDT 2013},
month = {Fri Sep 20 00:00:00 EDT 2013}
}

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Cited by: 7 works
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Works referenced in this record:

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Works referencing / citing this record:

Mask-based approach to phasing of single-particle diffraction data
journal, January 2016


Long-wavelength Mesh&Collect native SAD phasing from microcrystals
journal, February 2019


Merging of synchrotron serial crystallographic data by a genetic algorithm
text, January 2016


Long-wavelength Mesh&Collect native SAD phasing from microcrystals
text, January 2019