SIMULATIONS OF NUCLEATION AND EARLY GROWTH-STAGES OF PROTEIN CRYSTALS

Analysis of known protein crystal structures reveals that interaction energies between monomer pairs alone are not sufficient to overcome en tropy loss related to fixing monomers in the crystal lattice. Interact ions with several neighbors in the crystal are required for stabilizat ion of monomers in the lattice. A microscopic model of nucleation and early growth stages of protein crystals, based on the above observatio ns, is presented. Anisotropy of protein molecules is taken into accoun t by assigning free energies of association (proportional to the burie d surface area) to individual monomer-monomer contacts in the lattice. Lattice simulations of the tetragonal lysozyme crystal based on the m odel correctly reproduce structural features of the movement of disloc ation on the (110) crystal face. The dislocation shifts with the speed equal to the one determined experimentally if the geometric probabili ty of correct orientation is set to 10(-5), in agreement with previous ly published estimates. At this value of orientational probability, th e first nuclei, the critical size of which for lysozyme is four monome rs, appear in 1 ml of supersaturated solution on a time scale of micro seconds. Formation of the ordered phase proceeds through the growth of nuclei (rather then their association) and requires nucleations on th e surface at certain stages.