RUI: Solubility and Dynamic Implications for Structurally Homologous Disaccharides

With support from the Chemical Structure, Dynamics, and Mechanisms A (CSDM-A) Program in the Division of Chemistry, Christina Othon from Ripon College along with Patrick Willoughby from Ripon College and Erika Taylor from Wesleyan University will use both experiments and computational methods to study the stability of disaccharides in solution. The hydration and dynamical properties of disaccharides impact how these molecules stabilize proteins. Dr. Othon and her team will integrate molecular dynamics simulations, biophysical assays, and ultrafast spectroscopy to study the hydration and dynamical properties of glucose-based disaccharides in solution so that impacts on solubility, hydrogen bonding capacity, and the energetic and kinetic changes the molecules impart to the solvent can be learned. Undergraduate and graduate students will be trained in these research activities and this will be supplemented by the development of coursework training modules and workshop activities. Direct evidence of solvent-mediated osmolyte stabilization of proteins is important for understanding how thermal and other environmental stress fluctuations influence the stability and function of these important biomacromolecules. Computational docking models, circular dichroism, and calorimetry measurements will be used to investigate how disaccharides and their stereoisomers differ in their ability to stabilize protein structure. Hydration dynamics will then be evaluated using ultrafast fluorescence frequency up-conversion spectroscopy. This combination and computational and experimental approaches are expected to result in a molecular level understanding of the preferential solvation model regarding relevant protein-solute and solute-induced solvent modification for osmolyte stabilization. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.