1Electron Density Representation and Real-Space Refinement (New tricks from an old dog)

The expected electron density for an atomic model is calculated directly from the coordinates in a resolution-dependent manner. Several applications are discussed. Firstly, it is possible to refine atomic models in real-space, by optimizing the fit of the model to a map. The methods are conceptually similar to those of Diamond [Acta Crystallogr., 1971. A27: p. 436-452], but much improved through modeling of the resolution limits and inclusion of stereochemical restraints. The methods have been used for complete refinement of virus structures, for local refinement to enhance model-building, and as a pre-refinement method to improve the refinements of proteins by conventional reciprocal-space methods. Secondly, improved local measures of quality can be calculated, comparing the calculated and observed electron densities. Finally, the refinement methods can be applied at about 30 Å resolution to optimally fit known atomic structures into electron microscope reconstructions of large macromolecular complexes