The formation of a cation-stabilized guanine quadruplex (G-DNA) stem is an exceptionally slow process involving complex kinetics that has not yet been characterized at atomic resolution. Here, we investigate the formation of a parallel stranded G-DNA stem consisting of four strands of d(GGGG) using molecular dynamics simulations with explicit inclusion of counterions and solvent. Due to the limitations imposed by the nanosecond timescale of the simulations, rather than watching for the spontaneous formation of G-DNA, our approach probes the stability of possible supramolecular intermediates (including two-, three-, and four-stranded assemblies with out-of-register base pairing between guanines) on the formation pathway. The simulations suggest that "cross-like" two-stranded assemblies may serve as nucleation centers in the initial formation of parallel stranded G-DNA quadruplexes, proceeding through a series of rearrangements involving trapping of cations, association of additional strands, and progressive slippage of strands toward the full stem. To supplement the analysis, approximate free energies of the models are obtained with explicit consideration of the integral cations. The approach applied here serves as a prototype for qualitatively investigating other G-DNA molecules using molecular dynamics simulation and free-energy analysis.

• MeSH
• časové faktory MeSH
• DNA chemie   MeSH
• G-kvadruplexy MeSH
• guanin chemie   MeSH
• ionty MeSH
• kationty MeSH
• kinetika MeSH
• konformace nukleové kyseliny MeSH
• molekulární konformace MeSH
• molekulární modely MeSH
• oligonukleotidy chemie   MeSH
• sodík chemie   MeSH
• software MeSH
• teplota MeSH
• termodynamika MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• DNA MeSH
• guanin MeSH
• ionty MeSH
• kationty MeSH
• oligonukleotidy MeSH
• sodík 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