The molecular replacement method

Abstract

Molecular replacement can be used for obtaining approximate phasing of an unknown structure from a known related molecule and for phase improvement as well as extension in the presence of noncrystallographic symmetry. Emphasis is placed on the latter procedure. It is shown that the real-space method of iterative electron density averaging and Fourier back transformation corresponds to iterative phase substitution in the right-hand side of expressions to give a set of improved phases. Analysis of these expressions (the 'molecular replacement equations') provides insight into the limits of possible phase extension, and the implications for the use of calculated structure factors when there are no observed amplitudes. It is shown that the percentage of observed data and inaccuracy of the observed amplitudes available for phase extension are compensated by the extent of noncrystallographic redundancy and the fraction of crystal cell volume that may be flattened because it is outside the control of noncrystallographic symmetry.