Roles of electrostricted and structural hydration in the stability of nucleic acid duplexes.

Abstract

To understand the mechanisms that govern the many biological roles of nucleic acids, it is essential to have a complete physical description of the folding of nucleic acids, including ion and water binding. To investigate the role of water in the stability of nucleic acid duplexes, we use biophysical techniques such as differential scanning calorimetry (DSC and PPC), density, ultrasound and temperature-dependence UV spectroscopy to measure complete thermodynamic profiles for the unfolding of DNA hairpins and duplexes containing chemical modifications. The favorable folding of a DNA duplex (negative ΔGo) results from a compensation between a favorable ΔH and unfavorable TΔS contributions. The resulting compensating temperatures are characteristic of the type of hydration, electrostricted or structural. DSC and UV melting curves of DNA duplexes as a function of salt and osmolyte concentrations show ion and water releases. Therefore, the favorable folding of each DNA molecule results from the formation of base-pair stacks and uptake of both counterions and water molecules. Furthermore, the comparison of the signs of ΔΔGo (or ΔΔH-Δ(TΔS) compensation) with ΔΔV of the Hess cycles for pairs of duplexes with and without a chemical modification (base pair, bulge, mismatch or adduct), allow us to indicate the type of hydration of the chemical modification: similar signs indicate electrostricted hydration while opposite signs indicate structural hydration. The main conclusion is the incorporation of stabilizing chemical modifications in DNA is accompanied by an immobilization of electrostricted water while the incorporation of destabilizing modifications immobilizes structural water. Supported by Grant MCB-1912587 from National Science Foundation.