Thermodynamics and the structure of biological macromolecules

In this review, I will discuss the role of thermodynamics in both the determination and evaluation of the structure of biological macromolecules. The presentation relates to the historical context, state-of-the-art and projection into the future. Fundamental features relate to the effect of charge, exemplified in the study of synthetic and natural polyelectrolytes. Hydrogen bonding and water structure constitute basic aspects of the medium in which biological reactions occur. Viscosity is a classical tool to determine the shape and size of biological macromolecules. The thermodynamic analysis of multicomponent systems is essential fo the correct understanding of the behavior of biological macromolecules in solution and for the evaluation of results from powerful experimental techniques such as ultracentrifugation, light, X-ray and neutron scattering. The hydration, shape and flexibility of DNA have been studied, as well as structural transitions in nucleosomes and chromatin. A particularly rewarding field of activity is the study of unusual structural features of enzymes isolated from the extreme halophilic bacteria of the Dead Sea, which have adapted to saturated concentrations of salt. Future studies in various laboratories will concentrate on nucleic-acid--protein interactions and on the so-called 'crowding effect', distinguishing the behavior in bacteria, or other cells, from simple test-tube experiments.