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.

Computational analysis of complete gas-phase potential energy and free energy surfaces of the adenine···thymine base pair has been carried out. The study utilizes a combination of molecular dynamics simulations performed with Cornell et al. empirical force field and quenching technique. Twenty seven energy minima have been located at the potential energy surface of the adenine···thymine base pair:  nine of them are H-bonded structures, eight are T-shaped dimers, and the remaining nine correspond to various stacked arrangements. H-bonded structures are the most stable while stacked and T-shaped structures are by more than 4 kcal/mol less stable than the global minimum. The global minimum and the first two local minima utilize N9−H and N3 groups of adenine for the binding, i.e., the amino group N6, and ring N1 and N7 adenine positions are not involved in the base pairing. The most stable H-bonding patterns cannot occur in nucleic acids since the N9 position is blocked by the attached sugar ring. Hoogsteen and Watson−Crick type structures (third and fourth local minima) are by about 3 kcal/mol less stable than the global minimum. Energetic preferences of the global minimum and first two local minima were confirmed by correlated MP2 ab initio calculations with 6-31G** and 6-311G(2d,p) basis sets. Relative population of various structures (a quantity proportional to ΔG of base pair formation) was determined by molecular dynamics simulations in the NVE microcanonical ensemble. Although the stability order of the global and first two local minima is unaffected by including the entropy contribution, the stability order of the remaining structures is altered rather significantly in favor of stacked and T-shaped structures. The simulations further show that the population of the global minimum is about 35% and it means that experimental gas-phase studies are likely to detect a vast number of mutually coexisting structures.

The potential energy surface (PES) of the 9-methyladenine‚‚‚1-methylthymine (mA‚‚‚mT) nucleic acid base pair was investigated using molecular dynamics/quenching method utilizing the Cornell et al. (Cornell, W.

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