The average change of intensity due to adding a heavy atom to a protein crystal is calculated for both the centrie and the acentric reflections.The amount by which small shifts of the molecules change the intensities is obtained for the monoclinic and orthorhombie systems, and formulae are given for the changes caused by small translations and rotations of the molecules, by alterations of the lattice parameters, and by 'breathing' movements.The effects always increase linearly with 1/d.It is shown that quite small molecular shifts would interfere with the isomorphous-replacement method for proteins at the higher values of 1/d, but not at the lower values.
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Crick et al. (1956) studied this question.