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

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:
OSTI Identifier:
1255151
Report Number(s):
LA-UR--15-29209
Journal ID: ISSN 0907-4449; ABCRE6; PII: S0907444913018167
Grant/Contract Number:
AC52-06NA25396
Type:
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
Research Org:
Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
Sponsoring Org:
USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES experimental phasing; density modification; genetic algorithms