The interpretation of electron-density maps

The locations of peaks in small-molecule electron-density maps lead directly to a model of the atomic arrangement. This is then interpreted in terms of molecular structure, as will be described in Chapter 11. The interpretation of the electron-density maps of larger molecules may encounter one or more problems, some of which will be described. Such maps are rarely at atomic resolution. As a result, interpretation is somewhat more subjective than is the interpretation of the electron-density maps of small molecules. 

The mutiipte-isomorphous replacement (MIR) map has been calculated. Polyalanine IS fit to the map on a graphics system. Side chains can also be looked for if the sequence ts known. 

Symmetry averaging and solvent flattening to obtain more interpretable maps. 

Refine by least-squares techniques or X-PLOR at end of least-squares refinement. Use simulated annealing because more ability to move than in least squares. Raise temperature, therefore can sample different conformations. 

If model still in doubt use OMIT maps and difference maps and rebuild. 

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It should be clearly understood that such models cannot be accorded the same confidence that is placed in models fit directly to electron density maps.17 Although the interpretation of electron density maps is subjective and may even be distasteful to those with a more objective bent, it must be emphasized that the contribution of such maps to our understanding of the structure and function of protein molecules is so great that it is essential to extract all possible information from them. 

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