Cosolute Interactions with Nucleic Acids
Jeff Schwinefus - Associate Professor
For several years Professor Greg Muth and I have collaborated to explore the stability of folded 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. Using UV-absorbance, differential scanning calorimetry, and vapor pressure osmometry, we have been able to calculate 1.) the excess (or deficiency) of these cosolutes in a local domain near the surface of a nucleic acid relative to bulk solution, 2.) the amount of cosolute at the newly exposed surface area of an unfolded nucleic acid structure, and 3.) the hydration of nucleic acids. All of these calculations are important (especially 2.) to rationalize why these cosolutes destabilize nucleic acid folded structures. However, thermodynamic measurements do not provide information about specific interactions between cosolute and nucleic acid. What specific chemical functional groups on the nucleic acid do these cosolutes interact with? How do these cosolutes affect nucleic acid hydration?
To answer these questions, students working with me will simulate nucleic acids, from nucleotide monophosphates to DNA and RNA duplexes to larger RNA structures, in aqueous solutions using Amber, a molecular dynamics software package. Molecular dynamics simulates atomic motion as a function of time for all of the water, nucleic acid, and cosolute atoms in the simulation. These simulations have the benefit of allowing us to visualize interactions between water, cosolute, and nucleic acid as well as calculate the lifetime of these interactions to provide a molecular basis for our experimental measurements.