Lattice simulations of protein crystal formation

A new algorithm is presented for the lattice simulation of protein crystal growth. The algorithm allows the calculation of the size distribution of mi crocrystals in the volume and timescale of experiments and within the frame work of the previously-published microscopic model [A.M. Kierzek, W.M. Wolf , P. Zielenkiewicz, Biophys. J. 73 (1997) 571-580]. Simulations for the tet ragonal lysozyme crystal show that there are two critical sizes in the deve lopment of ordered phase. The first one corresponds to the size of the smal lest stable complex which, in the case of the tetragonal lysozyme crystal, is the particular tetramer. In a volume of 5 mu l the tetramer appears in t he millisecond timescale. The second critical radius of approximately 100 m onomers is only reached by a few of all the smallest stable complexes forme d in the solution. The model predicts that out of 10(7) tetramers which app ear in solution, only eight reach the size of 100 monomers within 8 h. Afte r exceeding the second critical radius the microcrystals grow to the size o f 10(4) monomers in the minute timescale and are thus assumed to quickly le ad to macroscopic crystals. The predicted number of crystals formed during 8 h of nucleation is in qualitative agreement with arrested nucleation expe riments. (C) 1999 Elsevier Science B.V. All rights reserved.