Significance of crystal growth of proteins and nucleic acids in biology: Novel ways in crystallogenesis

Until recently crystallization of macromolecules was rather empirical. Stimulated by developments of biotechnology and by the crystallization programs under microgravity, this empirical field is moving towards the new discipline of biological crystallogenesis, which includes biology, physics, crystallography and related engineering aspects. Here we will discuss attempts to control better the physical basis of the crystallization of biological macromolecules and to set up in a rational way crystal growth conditions. A micromethod for phase diagram determination is presented. It was established with concanavalin A and it shows that solubility curves are rather complex. The potentialities of quasi-elastic light scattering, as a diagnostic to find suitable solvent conditions for crystallization is shown. Finally the use of micropotentiometric methods to monitor equilibration kinetics and pH changes in vapor phase crystallization is presented. Because biological macromolecules are often not available in large quantity, these methods were established at microscales. Special emphasis is also given to the concept of purity of the macromolecules.