The crystal structure of d(CATGGGCCCATG)(2) shows unique stacking patterns of a stable B<-->A-DNA intermediate. We evaluated intrinsic base stacking energies in this crystal structure using an ab initio quantum mechanical method. We found that all crystal base pair steps have stacking energies close to their values in the standard and crystal B-DNA geometries. Thus, naturally occurring stacking geometries were essentially isoenergetic while individual base pair steps differed substantially in the balance of intra-strand and inter-strand stacking terms. Also, relative dispersion, electrostatic and polarization contributions to the stability of different base pair steps were very sensitive to base composition and sequence context. A large stacking flexibility is most apparent for the CpA step, while the GpG step is characterized by weak intra-strand stacking. Hydration effects were estimated using the Langevin dipoles solvation model. These calculations showed that an aqueous environment efficiently compensates for electrostatic stacking contributions. Finally, we have carried out explicit solvent molecular dynamics simulation of the d(CATGGGCCCATG)(2) duplex in water. Here the DNA conformation did not retain the initial crystal geometry, but moved from the B<-->A intermediate towards the B-DNA structure. The base stacking energy improved in the course of this simulation. Our findings indicate that intrinsic base stacking interactions are not sufficient to stabilize the local conformational variations in crystals.

• MeSH
• DNA chemistry   genetics   metabolism   MeSH
• Crystallization MeSH
• Models, Molecular MeSH
• Pliability MeSH
• Base Pairing * MeSH
• Computer Simulation * MeSH
• Solvents MeSH
• Base Sequence MeSH
• Static Electricity MeSH
• Thermodynamics MeSH
• Water chemistry   metabolism   MeSH
• Base Composition MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• DNA MeSH
• Solvents MeSH
• Water MeSH

Base-stacking interactions in canonical and crystal B-DNA and in Z-DNA steps are studied using the ab initio quantum-chemical method with inclusion of electron correlation. The stacking energies in canonical B-DNA base-pair steps vary from -9.5 kcal/mol (GG) to -13.2 kcal/mol (GC). The many-body nonadditivity term, although rather small in absolute value, influences the sequence dependence of stacking energy. The base-stacking energies calculated for CGC and a hypothetical TAT sequence in Z-configuration are similar to those in B-DNA. Comparison with older quantum-chemical studies shows that they do not provide even a qualitatively correct description of base stacking. We also evaluate the base-(deoxy)ribose stacking geometry that occurs in Z-DNA and in nucleotides linked by 2',5'-phosphodiester bonds. Although the molecular orbital analysis does not rule out the charge-transfer n-pi* interaction of the sugar 04' with the aromatic base, the base-sugar contact is stabilized by dispersion energy similar to that of stacked bases. The stabilization amounts to almost 4 kcal/mol and is thus comparable to that afforded by normal base-base stacking. This enhancement of the total stacking interaction could contribute to the propensity of short d(CG)n sequences to adopt the Z-conformation.

• MeSH
• Models, Chemical MeSH
• Deoxyribose MeSH
• DNA chemistry   MeSH
• Calorimetry MeSH
• Nucleic Acid Conformation * MeSH
• Quantum Theory MeSH
• Models, Molecular MeSH
• Oligodeoxyribonucleotides chemistry   MeSH
• Potentiometry MeSH
• Base Sequence MeSH
• Thermodynamics MeSH
• Base Composition MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Comparative Study MeSH
• Names of Substances
• Deoxyribose MeSH
• DNA MeSH
• Oligodeoxyribonucleotides MeSH