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Density Modification in X-Ray Crystallography

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Crystallographic Methods and Protocols

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 56))

Abstract

Crystallographic models are built by interpretation of an experimental image, the electron density map. This map is generally calculated from amplitudes measured experimentally and phases obtained with the multiple isomorphous replacement method. This method has poor precision, generating errors in the phases and therefore in the map. If the quality of the map is not sufficient to trace clearly a molecular model, it is necessary to improve the phases in order to obtain an interpretable map. Density modification methods achieve this by the application of physically meaningful constraints in real space, such as positivity, boundedness, electron density histograms, atomicity at high resolution, uniformity of solvent regions, continuity of the bio-polymer chain, and known noncrystallographic symmetry of the density distribution. To impose the physical constraints on an experimental map, an iterative algorithm has been proposed (1,2). It alternates real and reciprocal space operations, and merges gradually the physical constraints with the initial amplitudes and phases.

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Notes

  1. 1.

    It should be noted that a correct synthesis at finite resolution does not strictly have a constant level in the solvent region, owing to series termination errors and to partial ordering of the solvent molecules (12) This is clearly shown by electron density histogram analysis (7,13), and better modelization can be obtained, for example, by distance-to-boundary modulation of this density (14,15) However, this effect is much smaller than the noise introduced by phase error, and therefore, the assumption of a flat solvent region is a good first approximation

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Authors and Affiliations

  1. UPR de Biologie Structurale, Université Louis Pasteur, Illkirch, C.U. de Strasbourg, France

    Alberto D. Podjarny, Bernard Rees & Alexandre G. Urzhumtsev

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  1. Alberto D. Podjarny
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  2. Bernard Rees
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  3. Alexandre G. Urzhumtsev
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Editors and Affiliations

  1. National Institute for Biological Standards and Control, Potters Bar, UK

    Christopher Jones  & Barbara Mulloy  & 

  2. Department of Biophysics, King’s College, London, UK

    Mark R. Sanderson

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Podjarny, A.D., Rees, B., Urzhumtsev, A.G. (1996). Density Modification in X-Ray Crystallography. In: Jones, C., Mulloy, B., Sanderson, M.R. (eds) Crystallographic Methods and Protocols. Methods in Molecular Biology™, vol 56. Humana Press. https://doi.org/10.1385/0-89603-259-0:205

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  • DOI: https://doi.org/10.1385/0-89603-259-0:205

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