The anionic sugar-phosphate backbone of nucleic acids substantially contributes to their structural flexibility. To model nucleic acid structure and dynamics correctly, the potentially sampled substates of the sugar-phosphate backbone must be properly described. However, because of the complexity of the electronic distribution in the nucleic acid backbone, its representation by classical force fields is very challenging. In this work, the three-dimensional potential energy surfaces with two independent variables corresponding to rotations around the alpha and gamma backbone torsions are studied by means of high-level ab initio methods (B3LYP/6-31+G*, MP2/6-31+G*, and MP2 complete basis set limit levels). The ability of the AMBER ff99 [Wang, J. M.; Cieplak, P.; Kollman, P. A. J. Comput. Chem. 2000, 21, 1049-1074] and parmbsc0 [Perez, A.; Marchan, I.; Svozil, D.; Sponer, J.; Cheatham, T. E.; Laughten, C. A.; Orozco, M. Biophys. J. 2007, 92, 3817-3829] force fields to describe the various alpha/gamma conformations of the DNA backbone accurately is assessed by comparing the results with those of ab initio quantum chemical calculations. Two model systems differing in structural complexity were used to describe the alpha/gamma energetics. The simpler one, SPM, consisting of a sugar and methyl group linked through a phosphodiester bond was used to determine higher-order correlation effects covered by the CCSD(T) method. The second, more complex model system, SPSOM, includes two deoxyribose residues (without the bases) connected via a phosphodiester bond. It has been shown by means of a natural bond orbital analysis that the SPSOM model provides a more realistic representation of the hyperconjugation network along the C5'-O5'-P-O3'-C3' linkage. However, we have also shown that quantum mechanical investigations of this model system are nontrivial because of the complexity of the SPSOM conformational space. A comparison of the ab initio data with the ff99 potential energy surface clearly reveals an incorrect ff99 force-field description in the regions where the gamma torsion is in the trans conformation. An explanation is proposed for why the alpha/gamma flips are eliminated so successfully when the parmbsc0 force-field modification is used.

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Flemingovo namesti 2 166 10 Prague 6 Czech Republic