Journal of Physical Chemistry A, Vol.105, No.51, 11560-11573, 2001
Cyclic adenine-, cytosine-, thymine-, and mixed guanine-cytosine-base tetrads in nucleic acids viewed from a quantum-chemical and force field perspective
We have carried Out a systematic stud), of hydrogen-bonded cyclic A, C, T, and mixed GCGC tetrads resembling conformations occurring in experimental tetraplex structures. using the B3LYP hybrid density functional (DFT) method and the MMFF and AMBER force fields to determine tetrad structures and interaction energies. The results are compared to G and U tetrads anal zed previously, thereby presenting a comprehensive overview of all cyclic tetrads formed from one base type only. in addition to the GCGC data, The DFT calculations indicate that the C tetrad is planar and the GCGC tetrad is nearly planar and correspond to local minima at C-4h and C-i symmetry, respectively. For A tetrads with N6-H6...N7 and with N6-H6...N1 H-bonds and for T tetrads, nonplanar structure,, are more stable than the planar ones, and among tile nonplanar structures, S-4-symmetric conformations are more stable than C-4 structures. Minima confirmed by frequency calculations are found for the planar C tetrad, the C-i-symmetric GCGC tetrad, the C-4-symmetric structure of the A tetrad with N6-H6...N7 H-bonds, and the S-4-symmetric T tetrad, in addition to the already known local minima of the S4-symmetric structure of the G tetrad and the planar U tetrad with C-H... 0 hydrogen bonds, The interaction energies (DeltaE(T)) corrected for deformation of tile babes in the tetrads range from -69.47 kcal/mol for the GCGC tetrad with three pairs of strong Watson-Crick type hydrogen bonds to -11.09 kcal/mol in the planar A tetrad having only a single N6-H62...N1 interbase hydrogen bond. With more than 18%, the largest cooperativity contribution to DeltaE is found for the C and G tetrads. The interaction energies derived from the MMFF and AMBER force field are similar to the DFT data for those tetrads having high interaction energies, whereas the relative deviations are much larger for weakly H-bonded tetrads.