Analysis of the conformational features of Watson–Crick duplex fragments by molecular mechanics and quantum mechanics methods

It is generally accepted that important features of the Watson–Crick duplex (WCD) originate from the molecular structure of its subunits. However, it is still unclear what properties of each subunit are responsible for significant features of the WCD structure. Computations of deoxydinucleoside monophosphate (dDMP) complexes with Na ions on the basis of the density functional theory (DFT) have shown that conformational properties of minimal single-stranded fragments of DNA play a pivotal role in the origin of the unique features of the WCD. The directionality of the sugar-phosphate backbone (SPB) and preferable ranges of its torsion angles combined with the difference in geometry between purines and pyrimidines have been found to define the nucleotide sequence dependence of the WCD three-dimensional structure. In this work, density functional theory computations were extended to minimal duplex fragments, that is, complementary dDMP (cdDMP) complexes with Na ions. Using several computational methods and various functionals, energy minima were searched for the BI conformation of cdDMP complexes with different nucleotide sequences. Two sequences were optimized using an ab initio method at the MP2/6-31++G** level of theory. An analysis of the SPB torsion angles, sugar-ring puckering, and mutual base positions in the optimized structures showed that the conformational features of cdDMP complexes with Na ions remained within the BI ranges and become more similar to the corresponding features that WCDs display in a crystal. Qualitatively, the main features of each cdDMP complex were invariant with different computational methods, although the values of certain conformational parameters could vary, but still within the limits that are typical of the corresponding family. Common functionals that are employed in DFT calculations were observed to overestimate the distance between base pairs, while MP2 computations and new complex functionals yielded structures with atom–atom contacts that are too close. Several energy minima that correspond to the BI conformation have been proven to exist for certain cdDMP complexes with Na ions, indicating that the topography of the potential energy surface is complex. This circumstance accounts for the variation of conformational parameters among duplex fragments with the same nucleotide sequence. The common AMBER and CHARMM molecular mechanics force fields reproduce many conformational characteristics of dDMPs and their complementary complexes with Na ions, but fail to reproduce certain details of the nucleotide sequence dependence of the WCD conformation.