Intrinsic Conformational Properties of Deoxyribonucleosides: Implicated Role for Cytosine in the Equilibrium Among the A, B, and Z Forms of DNA

Abstract

Structural properties of biomolecules are dictated by their intrinsic conformational energetics in combination with environmental contributions. Calculations using high-level ab initio methods on the deoxyribonucleosides have been performed to investigate the influence of base on the intrinsic conformational energetics of nucleosides. Energy minima in the north and south ranges of the deoxyribose pseudorotation surfaces have been located, allowing characterization of the influence of base on the structures and energy differences between those minima. With all bases, chi values associated with the south energy minimum are lower than in canonical B-DNA, while chi values 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 conformations of the nucleosides are <0.5 kcal/mol in the present calculations, except 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 contribute to the A form of DNA containing predominately GC-rich sequences. In the context of a B versus Z DNA equilibrium, deoxycytidine favors the Z form over the B form by 1.6 kcal/mol as compared with deoxythymidine, suggesting that the intrinsic conformational properties of cytosine also contribute to GC-rich sequences occurring in Z DNA with a higher frequency than AT-rich sequences. Results show that the east pseudorotation energy barrier involves 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 pseudorotation barrier are lower in pyrimidines as compared with purines, indicating that the intrinsic conformational properties associated with base may 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.

Interaction of low-energy electrons with the pyrimidine bases and nucleosides of DNA

“…41 For dT, we optimized the geometry at the MP2 / 6-31+ G͑d͒ level, that is, with the 6-31G͑d͒ basis set supplemented by a 1s1p set of diffuse Gaussians ͑for which we used the GAMESS default values͒ on the heavy atoms. Our MP2 / 6-31+ G͑d͒ geometry for dT is almost identical to that which we obtain at the MP2 / 6-31G͑d͒ level, which is in turn very similar to the MP2 / 6-31G͑d͒ geometry determined by Foloppe and MacKerell 49 for the "south" conformer of the furanose ring. For dC, we used the "south" MP2 / 6-31G͑d͒ geometry of Foloppe and MacKerell.…”

“…For dC, we used the "south" MP2 / 6-31G͑d͒ geometry of Foloppe and MacKerell. 49 The structures of the four molecules are shown in Fig. 1, which was generated using MOLDEN.…”

Interaction of low-energy electrons with the purine bases, nucleosides, and nucleotides of DNA

“…88͒ or GAUSSIAN 94. 89 MP2/6−31G͑d͒ geometries for dA and dG were taken from the work of Foloppe and MacKerell, 90 in both cases using the geometry optimized for the "south" pseudorotational conformer of the furanose ring, which predominates in B-type DNA. 90 To obtain a geometry for dAMP, we replaced the OH group attached to the 5Ј carbon in the dA geometry of Ref.…”

“…89 MP2/6−31G͑d͒ geometries for dA and dG were taken from the work of Foloppe and MacKerell, 90 in both cases using the geometry optimized for the "south" pseudorotational conformer of the furanose ring, which predominates in B-type DNA. 90 To obtain a geometry for dAMP, we replaced the OH group attached to the 5Ј carbon in the dA geometry of Ref. 90 with a H 2 PO 4 group, using bond distances and angles taken from our previously computed MP2/6−31G͑d͒ geometry for deoxyribose 5Ј-monophosphate 68 to fix the positions of the added atoms.…”

“…90 To obtain a geometry for dAMP, we replaced the OH group attached to the 5Ј carbon in the dA geometry of Ref. 90 with a H 2 PO 4 group, using bond distances and angles taken from our previously computed MP2/6−31G͑d͒ geometry for deoxyribose 5Ј-monophosphate 68 to fix the positions of the added atoms. The resulting structures are shown in Fig.…”