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 chemie   genetika   metabolismus   MeSH
• krystalizace MeSH
• molekulární modely MeSH
• ohebnost (fyzika) MeSH
• párování bází * MeSH
• počítačová simulace * MeSH
• rozpouštědla MeSH
• sekvence nukleotidů MeSH
• statická elektřina MeSH
• termodynamika MeSH
• voda chemie   metabolismus   MeSH
• zastoupení bazí MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA MeSH
• rozpouštědla MeSH
• voda 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
• chemické modely MeSH
• deoxyribosa MeSH
• DNA chemie   MeSH
• kalorimetrie MeSH
• konformace nukleové kyseliny * MeSH
• kvantová teorie MeSH
• molekulární modely MeSH
• oligodeoxyribonukleotidy chemie   MeSH
• potenciometrie MeSH
• sekvence nukleotidů MeSH
• termodynamika MeSH
• zastoupení bazí MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• srovnávací studie MeSH
• Názvy látek
• deoxyribosa MeSH
• DNA MeSH
• oligodeoxyribonukleotidy MeSH

Extensive circular dichroism studies have been conducted with the title polynucleotides under various solution conditions. The studies provided the following information: (i) The halogen atoms in place of thymine methyl hinder the isomerization into X-DNA. (ii) The brominated but not iodinated polynucleotide isomerizes into Z-DNA in concentrated NaCl+NiCl2. The transition takes place at lower NiCl2 concentrations than with poly(dA-dT). (iii) The iodinated polynucleotide forms an unusual conformation in aqueous solution in which it is very stable. It isomerizes from this conformer into the usual B-type double helix in concentrated ethanol solutions. The isomerization is a two-state cooperative process. (iv) Both title polynucleotides undergo still another two-state cooperative transition in trifluorethanol solutions presumably into A-DNA showing a rather unusual circular dichroism spectrum.

• MeSH
• cirkulární dichroismus MeSH
• idoxuridin chemie   MeSH
• konformace nukleové kyseliny * MeSH
• poly A-U chemie   MeSH
• poly dA-dT chemie   MeSH
• spektrální analýza MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• idoxuridin MeSH
• poly (dA-BrdU) MeSH Prohlížeč
• poly A-U MeSH
• poly dA-dT MeSH
• poly(dA-IdU) MeSH Prohlížeč