The Hydration Properties of Proteins and Nucleic Acids
The majority of all biological processes involving proteins and nucleic acids occur in aqueous milieu. Consequently, it is not surprising that water plays a vital role in structural stability and functional activity of these biopolymers, including many important molecular recognition events. Hydration studies are of paramount importance for any complete thermodynamic description of the forces responsible for protein and nucleic acid recognition.
My work is aimed at physico-chemical characterizations of the hydration properties of proteins and nucleic acids as well as their complexes. The two key techniques which are used most widely in our hydration studies are the high precision densimetry (density measurements) and the novel method of ultrasonic velocimetry (ultrasonic velocity measurements). At present, the combination of densimetric and ultrasonic velocimetric techniques provides one of the most sensitive and informative means to characterize solute hydration in dilute solutions. In our studies, we combine the data provided by ultrasonic velocimetry and high precision densimetry with the data provided by differential scanning calorimetry, fluorscence spectroscopy, circular dichroism spectroscopy, and optical absorbance spectroscopy. While volumetric methods provide a unique insight into the hydration phenomenon, optical spectroscopic techniques provide structural information about the solute and calorimetric data allow one to gain insight into the energetics of a solute molecule.
Currently, my research activities are focused on the following three interrelated projects: (i) characterization of the hydration properties of globular proteins in their different conformational states (native, molten globule, unfolded); (ii) characterization of the hydration properties of nucleic acids; (iii) thermodynamics of ligand-protein and protein-protein association; and (iv) characterization of changes in hydration accompanying drug-DNA interactions. In my subsequent studies, I will further use the combination of volumetric, calorimetric, and spectroscopic techniques to investigate hydration aspects of other processes of biological significance, in particular, protein-DNA recognition and ligand-protein binding. On a practical level, the basic knowledge which can be gained from such hydration studies will find its applications in pharmaceutics and biotechnology. Ultimately, understanding of the “hydration energetics” of proteins and nucleic acids at the molecular level will facilitate the development of new drugs specifically targeted to selected sites of biopolymers and help in the design of modified proteins with predictably altered structures.
Leslie Dan Faculty of Pharmacy
University of Toronto
144 College Street
Toronto, Ontario, M5S 3M2