SEARCH DESIGNS FOR PROTEIN CRYSTALLIZATION BASED ON ORTHOGONAL ARRAYS

In protein crystallography, the initial experimental problem is the id entification of physical and chemical conditions that will support nuc leation and crystal growth. Ideally, experiments to search for such co nditions would be based on a full-factorial structure, with variation in the temperature and solution composition. However, consideration of even a moderate number of possibilities for the composition of the sy stem will result In factorial experiments which may be prohibitively l arge. In this paper it is proposed that search experiments for protein crystallization might be based on orthogonal arrays. These are subset s of full-factorial experiments which possess a great deal of symmetry , such that a uniform distribution of points throughout the experiment al region is preserved. Such experiments have reasonable size, explore the proposed experimental region in a systematic fashion, and form a logical basis for a sequential approach-to the search for crystallizat ion conditions. Examples of such initial search experiments are given, and their application to some recent protein crystallization problems in this laboratory is described briefly. The relationship of this app roach to other protein crystallization search procedures is also discu ssed.