COMO: a program for combined molecular replacement

The combined molecular-replacement protocol uses a limited six-dimensional search to solve a structure by the molecular-replacement method, with the s ampling of the rotational degrees of freedom guided by the rotation functio n. This protocol therefore automatically combines the information on the ro tational and translational parameters of the search model. The combined mol ecular-replacement protocol has been implemented in a new computer program, COMO. The calculation of the Patterson correlation translation function ha s been optimized to improve its speed performance. A packing check is imple mented that automatically removes impossible solutions and thereby increase s the signal in the calculation. A family of atomic models can be used as t he search model; the program will automatically select the model that gives the best result. The command interface is well organized and requires the definition of only a few critical parameters by the user. In addition, a gr aphical user interface has been constructed for the program. The program ha s been used to solve several difficult molecular-replacement problems. A ca se is presented where the program automatically determined the orientation and position of five copies of a search model in a high-symmetry space grou p.