Size Evolution and Composition of the Intermediate Phase During Nonclassical Protein Crystal Growth from Solution

We propose here that the intermediate nucleation phase identified in a certain case of protein crystal growth actually consists of two distinct parts: a low density and higher density phase. A theory for crystal growth is utilized to study the formation and growth of each phase. Within the framework of this theory, the low density phase is shown to obey a fourth order kinetic law, while the high density phase is zeroth order. The combination of these two phases is shown to be a good match for X-ray diffraction data, which is indicative of its presence. The crystal growth rate is then given in terms of the kinetic behavior of the intermediate nucleation phase. From this, the crystal radius is estimated and shown to compare favorably with reported size data. A method is proposed for determining the conditions that lead to protein crystals of the largest possible size.