Molecular replacement method at low resolution: optimum strategy and intrinsic limitations as determined by calculations on icosahedral virus models

An extensive series of phase refinements on model structure factors has been carried out to determine the scope and limitations of real-space symmetry averaging at low resolution. These calculations were used to derive and justify the strategy used to solve the structure of polyoma virus capsids at 22.5 Å resolution [Rayment, Baker, Caspar & Murakami (1982). Nature (London), 295, 110-115]. The calculations showed (1) that phases from a wide variety of models can be successfully refined; (2) a low R factor ( ~ 10%) between the constrained and observed amplitudes corresponds to a small error between the calculated and true phases; (3) on convergence to a low R factor there is no residual bias in the final phases introduced by the initial phasing model. The model calculations were also used to determine the limitations imposed by series termination, unmeasured data, random errors in the data and the role of the molecular envelope on the phase refinement.