WHY PROTEIN CRYSTALS FAVOR SOME SPACE-GROUPS OVER OTHERS

One of the most puzzling observations in protein crystallography is th at the various space-group symmetries occur with striking non-uniformi ty. Molecular close-packing has been invoked to explain similar observ ations for crystals of small organic compounds, but does not appear to be the dominant factor for proteins. Instead, we find that the observ ed frequencies for both two- and three-dimensional crystals can be exp lained by an entropic model. Under a requirement for connectivity, the favoured space groups are simply less restrictive than others in that they allow the molecules more rigid-body degrees of freedom and can t herefore be realized in a greater number of ways. This result undersco res the importance of the nucleation event in crystallization and lead s to specific ideas for crystallizing water-soluble and membrane prote ins.