Uracil Dimer:  Potential Energy and Free Energy Surfaces. Ab Initio beyond Hartree−Fock and Empirical Potential Studies

Abstract

The first complete theoretical analysis of the gas-phase formation of a nucleic acid base pair (uracil dimer) has been performed. The study is based on a combination of AMBER 4.1 empirical potential, correlated ab initio quantum chemical methods, computer simulations, and statistical thermodynamical methods. In total, 11 low-energy minima structures were located on the potential energy surface of the uracil dimer: seven of them are H-bonded, one is T-shaped, and three correspond to various stacked arrangements. The most stable structure is a H-bonded dimer with two N1−H···O2 H-bonds, designated as HB4; it has an energy minimum of −15.9 kcal/mol at the MP2/6-31G*(0.25)//HF/6-31G** level of theory. T-shaped structure and stacked structures are less stable than H-bonded ones. Thermodynamic characteristics were obtained using the rigid rotor−harmonic oscillator−ideal gas (RR-HO-IG) approximation adopting the AMBER 4.1 and ab initio characteristics. Furthermore, the population of various structures was determined by computer simulations in the NVT canonical and NVE microcanonical ensembles. Results obtained from the RR-HO-IG approximation and the NVT ensemble are very similar and differ from the result of the NVE ensemble. The present analysis demonstrates that different gas-phase experimental techniques can be used for investigating different regions of the conformational space for nucleic acid base pairs. The fact that entropy is always significant and differs for H-bonded and stacked structures is of importance.

Theoretical insights into the nature of intermolecular interactions in cytosine dimer

“…In the whole range of variability of slide parameter the C/C complex is stabilized only by dispersion and ∆E HF del terms. ε (12) el,r component is also of stabilizing character for slide values greater than -1 Å, while the first-order electrostatic contribution is of negative sign only for slide values less than 0.5 Å. Opposite to ε (10) el and ε (20) disp , ∆E (2) ex−del and ε HL ex do not exhibit strong dependence on the slide parameter.…”

“…The selected lowest-energy structure (BD0022) is characterized by rise value 3.53 Å . For this value of rise one finds, that besides significant stabilization due to the dispersion, the ε (12) el,r and ∆E del HF also contribute to the stabilization of the C/C complex. Figure 5 presents the relation between the interaction energy contributions and the roll and shift parameters.…”

“…The most important source of cytosine-cytosine complex stabilization is the dispersion contribution. However, ε (12) el,r component is also of stabilizng character for great majority of analyzed conformations of C/C complex. Interestingly, the first-order electrostatic term is repulsive in most of the considered configurations.…”

“…However, the exchange, dispersion and induction contributions also play an important role [7]. So far, the attention has been mainly focused on the calculations of the total stabilization energies of NAB complexes [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. It is well established that dispersion component is the main source of stabilization of stacked nucleic acid bases.…”

“…where ε (12) el,r denotes the term arising due to the dispersion and correlation corrections to the first-order electrostatic interacion, ε (20) disp is the dispersion contribution and ∆E (2) ex−del is the exchange-delocalization component.…”