[10] Dynamic light scattering in evaluating crystallizability of macromolecules.

In general, the factors important for protein crystallization are important for RNA crystallization, but there are additional factors that must be considered in RNA crystallization. Because most methods used to purify RNA denature the RNA, the annealing step is critical. The principal variables in the annealing are the temperature (40—70°C), incubation time at the highest temperature (1—10 minutes), cooling time (seconds to hours), buffer concentration and pH, and ionic composition (5—20 mM MgCl 2 ). Each annealing protocol could be subjected to the Sparse Matrix conditions. Alternatively, the annealing conditions can be optimized by monitoring the activity of the RNA or its chemical modification pattern 23 as conditions are varied. There are limitations to sampling the annealing condition. The buffers and ionic composition are partially determined by the Sparse Matrix. The annealing solutions (A.l—A.9) are usually made from desalted RNA stock solutions, but they can be made from solutions containing additional salts or polyamines. When considering the ionic composition of the solution,