Abstract
In the past decade macromolecular crystallography has undergone major advances in crystallization, data collection by synchrotron X-ray sources and area detectors, and data analysis by high performance computers and new computational techniques. In addition, recombinant gene technology in many cases allows the expression of large amounts of protein. This has resulted in an unprecedented increase in the number of protein crystal structures elucidated. Despite these successes, the fundamental problem in X-ray crystallography, the phase problem, remains unchanged. From a monochromatic diffraction experiment of a single crystal, it is possible to obtain the amplitudes, but not the phases of the reflections. Construction of the electron density by Fourier transformation requires both components of the complex structure factors. Phase information has to be obtained through experimental procedures, most commonly multiple isomorphous replacement, or knowledge-based procedures referred to as Patterson search or molecular replacement. Phase information obtained through these techniques is usually of limited accuracy and resolution, making it often difficult to interpret electron density maps in certain regions of the molecule. Furthermore, macromolecular crystals mostly diffract to less than atomic resolution, causing the process of fitting an atomic model to the observed intensities to be underdetermined.
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Brünger, A.T. (1996). Recent Developments for Crystallographic Refinement of Macromolecules. In: Jones, C., Mulloy, B., Sanderson, M.R. (eds) Crystallographic Methods and Protocols. Methods in Molecular Biology™, vol 56. Humana Press. https://doi.org/10.1385/0-89603-259-0:245
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DOI: https://doi.org/10.1385/0-89603-259-0:245
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