Combined molecular replacement

Current molecular-replacement methods assume that the correct rotations to be applied to a search atomic model are close to peaks in the rotation function. In addition, generally only the top peaks in the rotation function are examined by the translation function. For difficult structures and for high-symmetry space groups, this assumption may no longer hold true. The more powerful approach is to examine not only the peaks but also other angles that have reasonable values in the rotation function to look for the molecular-replacement solutions. The combined molecular-replacement protocol is therefore a limited six-dimensional search, where the sampling of the rotational degrees of freedom is restricted by the rotation function. A packing check is used to eliminate solutions that cause steric clashes of the search atomic model in the crystal. Several new structures have been determined with this protocol.