For protein crystals in which more than two thirds of the volume is occupied by solvent, the featureless nature of the solvent region often generates a constraint that is powerful enough to allow direct phasing of X-ray diffraction data. Practical implementation relies on the use of iterative projection algorithms with good global convergence properties to solve the difficult nonconvex phase-retrieval problem. In this paper, some aspects of phase retrieval using iterative projection algorithms are systematically explored, where the diffraction data and density-value distributions in the protein and solvent regions provide thesole constraints. The analysis is based on the addition of random error to thephases of previously determined protein crystal structures, followed by evaluation of the ability to recover the correct phase set as the distance from the solution increases. The properties of the difference-map (DM), relaxed-reflect-reflect (RRR) and relaxed averaged alternating reflectors (RAAR) algorithms are compared. All of these algorithms prove to be effective for crystallographic phase retrieval, and the useful ranges of the adjustable parameter which controls their behavior are established. When these algorithms converge to the solution, the algorithm trajectory becomes stationary; however, the density function continues to fluctuate significantly around its mean position. It is shown that averaging over the algorithm trajectory in the stationary region, following convergence, improves the density estimate, with this procedure outperforming previous approaches for phase or density refinement.
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