Intrinsic Conformational Energetics Associated with the Glycosyl Torsion in DNA: A Quantum Mechanical Study

Abstract

The glycosyl torsion (chi) in nucleic acids has long been recognized to be a major determinant of their conformational properties. chi torsional energetics were systematically mapped in deoxyribonucleosides using high-level quantum mechanical methods, for north and south sugar puckers and with gamma in the g(+) and trans conformations. In all cases, the syn conformation is found higher in energy than the anti. When gamma is changed from g(+) to trans, the anti orientation of the base is strongly destabilized, and the energy difference and barrier between anti and syn are significantly decreased. The barrier between anti and syn in deoxyribonucleosides is found to be less than 10 kcal/mol and tends to be lower with purines than with pyrimidines. With gamma = g(+)/chi = anti, a south sugar yields a significantly broader energy well than a north sugar with no energy barrier between chi values typical of A or B DNA. Contrary to the prevailing view, the syn orientation is not more stable with south puckers than with north puckers. The syn conformation is significantly more energetically accessible with guanine than with adenine in 5-nucleotides but not in nucleosides. Analysis of nucleic acid crystal structures shows that gamma = trans/chi = anti is a minor but not negligible conformation. Overall, chi appears to be a very malleable structural parameter with the experimental chi distributions reflecting, to a large extent, the associated intrinsic torsional energetics.

Selection of G‐Quadruplex Folding Topology with LNA‐Modified Human Telomeric Sequences in K+ Solution

“…To avoid artefacts from hydrogen bonding of the 5'-and 3'-hydroxy groups, the backbone torsion angles were kept at the values found in helical fragments. The profile obtained for the DNA nucleoside is similar to that obtained by Foloppe et al, [35,36] with a global minimum in the anti range at 2348 and a local minimum in the syn range at around 708. Upon introduction of a 2'-oxygen, the minimum in the anti range shifts to 1748 and 1928 for the RNA and LNA nucleosides, respectively.…”

Direct Measurement of Sequence-Dependent Transition Path Times and Conformational Diffusion in DNA Duplex Formation

“…It is known, for example, that G can adopt the syn conformation of the glycosidic bond between the base and the backbone more readily than other nucleotides, such as in Z-DNA (59). The energy barrier for syn/anti isomerization is predicted to be lower for purines than pyrimidines (60), and the isomerization rate was observed to be faster for G than A (61). Calculations of dinucleoside energies in torsion angle hyperspace also found generally broader energy minima for G:C-paired dinucleosides than A:T-paired ones (62).…”

The subgenomic promoter of brome mosaic virus folds into a stem–loop structure capped by a pseudo-triloop that is structurally similar to the triloop of the genomic promoter

“…Thus, fast syn/anti exchanges appear likely rather than fixed syn or anti glycosidic angles for these nucleotides. Such an equilibrium is feasible as the energy barrier to interconversion is low for nucleotides, especially purines, with a C29-endo sugar pucker (Foloppe et al 2002).…”