Thermodynamic Parameters for Stacking and Hydrogen Bonding of Nucleic Acid Bases in Aqueous Solution:  Ab Initio/Langevin Dipoles Study

Abstract

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 functions were used) and Langevin dipoles solvation model. The entropy contributions to the free energies for stacking and hydrogen bonding are approximated using the linear relationship between binding enthalpies and entropies determined here from the available experimental data. This methodology is used to evaluate the dependence of PMF, and the gas-phase and solvation energies on the twist angle (Ω) in a number of undisplaced face-to-back stacking complexes. Further, we characterized the vertical association of the parallel (Ω ) 0°) and antiparallel (Ω ) 180°) stacked cytosine dimers. The results show large compensation between the gas-phase and solvation energetics and an overall preference of the bases in the undisplaced face-to-back stacked complexes for the twist angles near 30°. An important exception from this trend involves the GC and CG complexes, for which the largest stabilization occurs for the twist angle near 180°. In addition, free energies for the formation of 27 hydrogen-bonded base pairs were determined and compared with their stacking counterparts. The calculated standard free energies for the formation of stacked and hydrogen-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‚cytosine base pair was found to be the most stable of all studied complexes. In agreement with the previous experimental findings, complexes containing purine bases were calculated to be more stable than their pyrimidine-containing counterparts.

Probing the Energetic and Structural Role of Amino Acid/Nucleobase Cation-π Interactions in Protein-Ligand Complexes

“…First, the ab initio energy computations were performed in vacuum and may not be directly transposed to more realistic environments consisting of water and/or protein residues. Ab initio energies of H-bonds and especially salt bridges are largely overestimated in vacuum compared with water (4, 39), whereas stacking interactions are less overestimated (39). In other words, electrostatic contributions, estimated at HF calculation level, are more overestimated than electron correla-tion contributions introduced at MP2 level.…”

Formamide and the origin of life

“…Energetically favorable stacking interactions between bases play an important role in determining and stabilizing nucleic acid structures [117,118]. The physical fundamentals of nucleic acid bases stacking in water have been accurately defined and reviewed [119][120][121], the thermodynamic parameters for stacking have been determined [122,123].…”

“…In particular, it was established that the stacked states have a 2-6 kcal mol lower free energy than the unstacked states for purine-purine dimers, while for pyrimidinepyrimidine dimers no appreciable barrier was obtained [124,126]. The most favorable stacking is found in A-A and G-G [120,122,123], determining their rapidly-obtained stacked state in the high dielectric aqueous solution [127]. The stacking-unstacking equilibrium has been characterized as a fundamental parameter in the nick sealing process in DNA [118].…”

Comparison of Intrinsic Stacking Energies of Ten Unique Dinucleotide Steps in A-RNA and B-DNA Duplexes. Can We Determine Correct Order of Stability by Quantum-Chemical Calculations?

“…However, it must be emphasized that regarding thermodynamics stability of DNA or RNA, the solvent screening compensates for the electrostatics interactions in both attractive and repulsive arrangements. 59,101 Thus the gas phase data, albeit important, cannot be directly used to assess the contribution of particular stacking interactions to the thermodynamics stability of nucleic acids.…”

“…The d-polarization functions are capable of filling the gap between the interacting monomers, which significantly improves the description of base stacking interactions compared with the standard 6-31G* basis set. The MP2/6-31G*(0.25) method has been the most widely used ab initio technique to study aromatic stacking in the past literature 31,35,50,51,60,85,100,101,[107][108][109][110][111][112][113][114][115][116][117][118][119][120] and has only recently been replaced by CBS(T). The MP2/6-31G*(0.25) method is entirely sufficient to capture the nature of base stacking, and therefore all conclusions reported with this method remain qualitatively valid.…”