Restrained real-space macromolecular atomic refinement using a new resolution-dependent electron-density function

A new atomic electron-density function is derived by Fourier transformation of resolution-truncated atomic scattering factors. It forms the basis of a new real-space refinement method, RSREF, that is a substantial improvement on prior implementations that did not formally consider the absence of high-resolution terms in a typical macromolecular electron-density map. Real-space refinement is further improved through the simultaneous refinement of stereochemical restraints analogous to reciprocal-space methods. Parallel refinements of a viral capsid structure show that real-space refinement produces models that are at least as good as those refined in reciprocal space, by either restrained or molecular-dynamics methods, and that refinement cycles are ~50 times faster. Real-space refinement will not replace reciprocal-space methods for proteins, where, without the high noncrystallographic symmetry of viruses, experimental phases and electron-density maps are not of the same high quality. However, applied to local regions, it can be used to speed up and improve the quality of interactive model building before a full refinement is started.