Ab initio structure solution of nucleic acids and proteins by direct methods: reciprocal-space and real-space approach

An ab initio method for solving macromolecular structures is described. The heavy atom(s) or some disulfide bridge in the structure are located from the phase sets selected on the basis of a figure of merit of a reciprocal-space-based multiple-solution direct method. Subsequent weighted Fourier recycling reveals recognizable structures for two nucleic acids where data resolution is 1.3 Å or better. With lower than 1.3 Å data resolution or sulfur as the heaviest atom in the structure, the phase refinement has been carried out using the density modification procedure (PERP) operating in direct space. The resulting electron density map can readily be interpreted. The methodology has been illustrated with six known nucleic acids and proteins crystallizing in different space groups. It has proved to be fast, simple to use and a very effective tool for solving macromolecular structures with data resolution up to 1.7 Å.