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

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The glycosyl torsion ( χ) in nucleic acids has long been recognized to be a major determinant of their conformational properties. χ torsional energetics were systematically mapped in deoxyribonucleosides using high-level quantum mechanical methods, for north and south sugar puckers and with γ in the g + and trans conformations. In all cases, the syn conformation is found higher in energy than the anti. When γ 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 γ = g +/ χ = anti, a south sugar yields a significantly broader energy well than a north sugar with no energy barrier between χ 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 γ = trans/ χ = anti is a minor but not negligible conformation. Overall, χ appears to be a very malleable structural parameter with the experimental χ distributions reflecting, to a large extent, the associated intrinsic torsional energetics.