Hydration Studies of Biological Macromolecules by Intermolecular Water-Solute NOEs

Conclusion

What have we learned from hydration studies of biological macromolecules using water-solute NOEs? Perhaps the most interesting result are the short residence times of the hydration water molecules on protein and DNA surfaces. Hydration-dehydration events would not be expected to be rate-limiting steps in protein folding and intermolecular recognition. Most of the water molecules detected by X-ray crystallography were shown not to be kinetically stable in solution. The possibility of obtaining this information for many individual water molecules in aqueous solution is unique to the NOE method. The hydration studies of proteins and other biological macromolecules by intermolecular water-solute NOEs certainly triggered the development of numerous new pulse sequences dedicated to the detection of intermolecular water-solute cross peaks. In the field of selective water excitation, the experiments with the most colorful acronyms are perhaps not the most attractive in practice. Yet the ideas developed in the context of biomolecular hydration studies may prove invaluable in the development of pulse sequences applicable to the study of ¹H-¹H NOEs between biological macromolecules and organic cosolvents in aqueous solutions. The first NOE studies of protein-organic solvent interactions are currently emerging (Liepinsh and Otting, 1997; Ponstingl and Otting, 1997a). They may significantly enhance our understanding of altered enzyme specificity observed in nonaqueous environments and provide a tool for rational drug design.

Reprinted from “Progress in Nuclear Magnetic Resonance Spectroscopy,” Vol. 31, Gottfried Otting, NMR Studies of Water Bound to Biological Molecules, pp. 259–285, 1997, with kind permission from Elsevier Science-NL, Sara Burgerhartstraat 25, 1055 KV Amsterdam, The Netherlands.

Editorial note: The exploitation of intermolecular water-solute NOEs in biological molecules was originally proposed in 1973 by N. Rama Krishna and Sidney L. Gordon in their study of the effects on solutes with coupled spin systems [J. Chem. Phys.58 (1973), 5687–5696]. The first demonstration of an intermolecular solvent-solute NOE dates back to 1965 when Reinhold Kaiser reported the observation of an enhancement in a chloroform proton signal when the solvent cyclohexane was saturated [J. Chem. Phys.42 (1965), 1838–1839].