Intrinsic conformational properties of deoxyribonucleosides: Implicated role for cytosine in the equilibrium among the A, B, and Z forms of DNA

Structural properties of biomolecules are dictated by their intrinsic confo rmational energetics in combination with environmental contributions. Calcu lations using high-level ab initio methods on the deoxyribonucleosides have been performed to investigate the influence of base on the intrinsic confo rmational energetics of nucleosides. Energy minima in the north and south r anges of the deoxyribose pseudorotation surfaces have been located, allowin g characterization of the influence of base on the structures and energy di fferences between those minima. With all bases, chi values associated with the south energy minimum are lower than in canonical B-DNA, while chi value s associated with the north energy minimum are close to those in canonical A-DNA. In deoxycytidine, chi adopts an A-DNA conformation in both the north and south energy minima. Energy differences between the A and B conformati ons of the nucleosides are <0.5 kcal/mol in the present calculations, excep t with deoxycytidine, where the A form is favored by 2.3 kcal/mol, leading the intrinsic conformational energetics of GC basepairs to favor the A form of DNA by 1.5 kcal/mol as compared with AT pairs. This indicates that the intrinsic conformational properties of cytosine at the nucleoside level con tribute to the A form of DNA containing predominately CC-rich sequences. In the context of a B versus Z DNA equilibrium, deoxycytidine favors the Z fo rm over the B form by 1.6 kcal/mol as compared with deoxythymidine, suggest ing that the intrinsic conformational properties of cytosine also contribut e to CC-rich sequences occurring in Z DNA with a higher frequency than AT-r ich sequences. Results show that the east pseudorotation energy barrier inv olves a decrease in the furanose amplitude and is systematically lower than the inversion barrier, with the energy differences influenced by the base. Energy barriers going from the south (B form) sugar pucker to the east pse udorotation barrier are lower in pyrimidines as compared with purines, indi cating that the intrinsic conformational properties associated with base ma y also influence the sugar pseudorotational population distribution seen in DNA crystal structures and the kinetics of B to A transitions. The present work provides evidence that base composition, in addition to base sequence , can influence DNA conformation.