Thermodynamic parameters for stacking and hydrogen bonding of nucleic acidbases in aqueous solution: Ab initio/Langevin dipoles study

The potentials of mean force (PMF) for the association of purine, adenine, thymine, guanine, cytosine, and uracil in aqueous solution are investigated using ab initio MP2/6-31G(d-0.25) calculations (diffuse d-polarization fun ctions were used) and Langevin dipoles salvation model. The entropy contrib utions to the free energies for stacking and hydrogen bonding are approxima ted using the linear relationship between binding enthalpies and entropies determined here from the available experimental data. This methodology is u sed to evaluate the dependence of PMF, and the gas-phase and salvation ener gies on the twist angle (Omega) in a number of undisplaced face-to-back sta cking complexes. Further, we characterized the vertical association of the parallel (Omega = 0 degrees) and antiparallel (Omega = 180 degrees) stacked cytosine dimers. The results show large compensation between the gas-phase and solvation energetics and an overall preference of the bases in the und isplaced face-to-back stacked complexes for the twist angles near 30 degree s. An important exception from this trend involves the GC and CG complexes, for which the largest stabilization occurs for the twist angle near 180 de grees. In addition, foe energies for the formation of 27 hydrogen-bonded ba se pairs were determined and compared with their stacking counterparts. The calculated standard free energies for the formation of stacked and hydroge n-bonded complexes at 298 K and neutral pH fell in a narrow region between 0.3 and -1.9 kcal/mol. Here, the hydrogen-bonded Watson-Crick guanine cytos ine base pair was found to be the most stable of all studied complexes. In agreement with the previous experimental findings, complexes containing pur ine bases were calculated to be more stable than their pyrimidine-containin g counterparts.