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Explaining the varied glycosidic conformational, G-tract length and sequence preferences for anti-parallel G-quadruplexes.

Cang X, Šponer J, Cheatham TE - Nucleic Acids Res. (2011)

Bottom Line: Structural polymorphisms of G-quadruplexes relate to these glycosidic conformational patterns and the lengths of the G-tracts.G3-tracts, on the other hand, cannot present this repeating pattern on each G-tract.This leads to smaller energy differences between different geometries and helps explain the extreme structural polymorphism of the human telomeric G-quadruplexes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.

ABSTRACT
Guanine-rich DNA sequences tend to form four-stranded G-quadruplex structures. Characteristic glycosidic conformational patterns along the G-strands, such as the 5'-syn-anti-syn-anti pattern observed with the Oxytricha nova telomeric G-quadruplexes, have been well documented. However, an explanation for these featured glycosidic patterns has not emerged. This work presents MD simulation and free energetic analyses for simplified two-quartet [d(GG)](4) models and suggests that the four base pair step patterns show quite different relative stabilities: syn-anti > anti-anti > anti-syn > syn-syn. This suggests the following rule: when folding, anti-parallel G-quadruplexes tend to maximize the number of syn-anti steps and avoid the unfavorable anti-syn and syn-syn steps. This rule is consistent with most of the anti-parallel G-quadruplex structures in the Protein Databank (PDB). Structural polymorphisms of G-quadruplexes relate to these glycosidic conformational patterns and the lengths of the G-tracts. The folding topologies of G2- and G4-tracts are not very polymorphic because each strand tends to populate the stable syn-anti repeat. G3-tracts, on the other hand, cannot present this repeating pattern on each G-tract. This leads to smaller energy differences between different geometries and helps explain the extreme structural polymorphism of the human telomeric G-quadruplexes.

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RMSD curves (Å) versus time (ps) for the SA-aabb (black), AA (red), AS (green) and 3AA + 1SS (blue) model simulations.
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Figure 4: RMSD curves (Å) versus time (ps) for the SA-aabb (black), AA (red), AS (green) and 3AA + 1SS (blue) model simulations.

Mentions: The all-atom RMSD values for the four two-quartet models over the MD trajectories are shown in Figure 4. The SA-aabb model remained close to the initial structure indicative of a stable trajectory throughout the 100 ns of MD simulation. The other two SA models, SA-abab and SA-aaab, were also built to test the influence of the arrangement of the four strands, and they also both sampled very stable trajectories as suggested by low RMSD (an average all-atom RMSD of 0.8 Å for SA-abab and 0.9 Å for SA-aaab) throughout 25-ns-length simulations.Figure 4.


Explaining the varied glycosidic conformational, G-tract length and sequence preferences for anti-parallel G-quadruplexes.

Cang X, Šponer J, Cheatham TE - Nucleic Acids Res. (2011)

RMSD curves (Å) versus time (ps) for the SA-aabb (black), AA (red), AS (green) and 3AA + 1SS (blue) model simulations.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3105399&req=5

Figure 4: RMSD curves (Å) versus time (ps) for the SA-aabb (black), AA (red), AS (green) and 3AA + 1SS (blue) model simulations.
Mentions: The all-atom RMSD values for the four two-quartet models over the MD trajectories are shown in Figure 4. The SA-aabb model remained close to the initial structure indicative of a stable trajectory throughout the 100 ns of MD simulation. The other two SA models, SA-abab and SA-aaab, were also built to test the influence of the arrangement of the four strands, and they also both sampled very stable trajectories as suggested by low RMSD (an average all-atom RMSD of 0.8 Å for SA-abab and 0.9 Å for SA-aaab) throughout 25-ns-length simulations.Figure 4.

Bottom Line: Structural polymorphisms of G-quadruplexes relate to these glycosidic conformational patterns and the lengths of the G-tracts.G3-tracts, on the other hand, cannot present this repeating pattern on each G-tract.This leads to smaller energy differences between different geometries and helps explain the extreme structural polymorphism of the human telomeric G-quadruplexes.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.

ABSTRACT
Guanine-rich DNA sequences tend to form four-stranded G-quadruplex structures. Characteristic glycosidic conformational patterns along the G-strands, such as the 5'-syn-anti-syn-anti pattern observed with the Oxytricha nova telomeric G-quadruplexes, have been well documented. However, an explanation for these featured glycosidic patterns has not emerged. This work presents MD simulation and free energetic analyses for simplified two-quartet [d(GG)](4) models and suggests that the four base pair step patterns show quite different relative stabilities: syn-anti > anti-anti > anti-syn > syn-syn. This suggests the following rule: when folding, anti-parallel G-quadruplexes tend to maximize the number of syn-anti steps and avoid the unfavorable anti-syn and syn-syn steps. This rule is consistent with most of the anti-parallel G-quadruplex structures in the Protein Databank (PDB). Structural polymorphisms of G-quadruplexes relate to these glycosidic conformational patterns and the lengths of the G-tracts. The folding topologies of G2- and G4-tracts are not very polymorphic because each strand tends to populate the stable syn-anti repeat. G3-tracts, on the other hand, cannot present this repeating pattern on each G-tract. This leads to smaller energy differences between different geometries and helps explain the extreme structural polymorphism of the human telomeric G-quadruplexes.

Show MeSH