Application of the molecular replacement method to multidomain proteins. 1. Determination of the orientation of an immunoglobulin Fab fragment.

Multidomain proteins provide special problems in the application of the molecular replacement method of structure determination. The structure of the Fab fragment from the autoimmune poly(dT)-specific antibody HED10 has been determined using molecular replacement. An analysis of the effects of varying the model and the parameters used in the rotation function indicates that dividing the molecule into individual relatively rigid domains simplifies interpretation of the results, and that the optimal parameters depend on the molecule under study.