DNA and RNA Folding Thermodynamics in Cosolute Solutions
Jeffrey Schwinefus - Associate Professor
For several years my students have explored the folding thermodynamics of nucleic acids, from simple, short DNA duplexes to complex RNA structures. Much of our effort has focused on the role that neutral organic molecules like urea or amino acids (which we generically call cosolutes) have in lowering the stability of folded nucleic acid structures. If cosolute interactions with the nucleic acid surface area exposed during unfolding is thermodynamically favorable, then the stability of nucleic acids will be lower relative to nucleic acids in purely aqueous solution. Using UV-absorbance, differential scanning calorimetry, solubility measurements, and vapor pressure osmometry, we have been able to determine 1.) the excess (or deficiency) of these cosolutes in a local domain near the surface of a nucleic acid relative to bulk solution and 2.) the amount of cosolute interacting with specific functional groups on the newly exposed surface area of an unfolded nucleic acid structure. All of these calculations are important to rationalize what functional groups on nucleic acid surfaces these cosolutes interact with to destabilize nucleic acid folded structures.
Our future research will focus on cosolute interactions with biologically-relevant DNA and RNA structures such as RNA hairpins, RNA bulged duplexes, and DNA G-quadruplexes. All of these structures provide unique solvent accessible surface areas for cosolute interactions that will help us refine our theories of cosolute attenuation of nucleic acid stability and contribute to the general understanding of biopolymer folding.