Considerations for the refinement of low-resolution crystal structures.

It is often assumed that crystal structures have to be obtained at sufficiently high resolution in order to perform macromolecular refinement. In several recent structures, the threshold of what is considered ;acceptable' has been pushed to lower diffraction resolutions. Here, considerations and modifications to standard refinement protocols are described that were used to solve and refine a particular set of low-resolution structures for the ATPase p97/VCP. It was found that reasonable R(free) values and good geometry can be achieved upon refinement that includes experimental phase information along with judicious use of restraints at diffraction limits as low as 4.7 A. At this resolution, the topology and the backbone-chain trace are mostly defined, some side-chain positions can be unambiguously assigned and ligands within known binding sites can be identified. Furthermore, large conformational changes can be discerned when structures in different states are available, information that is not easily obtainable by other means.