Stability of DNA duplexes with Watson-Crick base pairs: a predicted model

The conformational stability (difference between the free energies of the folded and unfolded states, DeltaG degrees ) of a DNA duplex is considered as a function of component energy terms, hydrophobic, base stacking, hydrogen bonding, van der Waals, and electrostatic, and a trinucleotide-level helix stiffness parameter measured in terms of its Young's modulus. Hydrophobic and base stacking energy components were determined with the use of the crystal structure data of 30 DNA duplexes judicially selected within a resolution of 1.5 A, and hydrogen bonding, van der Waals and electrostatic terms were determined through an extensive review of experimental and theoretical studies. The stiffness indices for the trinucleotides were the ones realized by M. M. Gromiha [(2000) J. Biol. Phys. 26, 43-50] using the crystal structure data of 70 DNA duplexes. The unfolded state was treated in the classical way to determine its stability. Thermodynamically determined DeltaG degrees values for 111 DNA duplexes, with the number of base pairs ranging from 4 to 16, were selected in two sets, and the regression equation formed with one set was used to predict the stabilities of the other set, taking the energy components and the stiffness parameter to be independent variables. The computed energy terms indicate that the base stacking and hydrogen bonding forces are the dominant and the hydrophobic and electrostatic forces the weak partners in imparting stability to the duplexes. This model predicts DeltaG degrees values for DNA duplexes examined with a level of accuracy similar to that used for predictions made by the widely used nearest-neighbor models. The uniqueness of this model is that it combines the crystal and thermodynamic data for interpretation of conformational stability.