Why Are There Errors in Crystal Structures

When presented with a structural file, one s initial temptation is to treat the contained coordinates as a direct 3D image of a protein stmcture the reality, however, is that the 

Copyright 2011 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-S27-32636-5 

To elucidate a crystal structure, a crystallographer collects a set of observed diffraction intensities for a crystal diffracting in an X-ray beam. The intensities alone, however, are insufficient to construct a model the crystallographer needs to predict a set of unknowns called the reflection phases. These are initially estimated by various techniques to give a starting model. The starting model is then refined, and the refined model is used to recalculate the phases, allowing the calculation of an improved electron density map, which can be reinterpreted. The process is cyclical, but hopefully leads to an accurate interpretation of the reflection intensities. 

Note that a pattern of X-ray intensities reflects the distribution of electrons in the underlying crystal. The atomic model is therefore an interpretation of this electronic distribution. One consequence of this is that elements can be misinterpreted in a model, as elements of a similar atomic number (such as carbon, nitrogen, and oxygen) can be used almost equally well to model regions of the electronic distribution. This problem is interlinked with the problem of structural resolution (see Section 4.5.2). A low resolution indicates that the underlying diflfraction data vfill be harder to interpret as an atomic model due to a lack of information content in the diffraction pattern. 

An additional problem with crystal structures that can give rise to a misleading model is the thermal motion and disorder within the crystalline lattice. Local regions of electron density can be poorly defined, even for structures with relatively good resolution if, for example, a protein residue is labile in the crystalline state. If undetected, a residue can be poorly modeled, misassigned, or omitted from the model. Even when detected and fully modeled, disorder implies flexibility, which may need specific handling in a docking study. 

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