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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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Six two-quartet models were investigated in this work: (a) SA-aabb, (b) SA-abab, (c) SA-aaab, (d) AA, (e) AS and (f) 3AA + 1SS. The notation ‘a’ and ‘b’ refers to the relative strand orientations. Yellow is for syn and blue is for anti glycosidic bond orientations. The channel cation (K+) is not shown.
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Figure 2: Six two-quartet models were investigated in this work: (a) SA-aabb, (b) SA-abab, (c) SA-aaab, (d) AA, (e) AS and (f) 3AA + 1SS. The notation ‘a’ and ‘b’ refers to the relative strand orientations. Yellow is for syn and blue is for anti glycosidic bond orientations. The channel cation (K+) is not shown.

Mentions: The definitive glycosidic bond conformational patterns observed along G-tracts led to our hypothesis that different glycosidic steps have different relative stabilities, and these differences in stability lead to the different glycosidic bond orientation patterns observed in anti-parallel G-quadruplexes. To test this hypothesis, we built up six two-quartet models (Figure 2) and performed explicit solvent molecular dynamics (MD) simulations with modern force field and simulation protocols. The simulation results provide an understanding of the relative free energies of different G-DNA syn/anti patterns and explain the structural polymorphism of particular G-quadruplex sequences.Figure 2.


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)

Six two-quartet models were investigated in this work: (a) SA-aabb, (b) SA-abab, (c) SA-aaab, (d) AA, (e) AS and (f) 3AA + 1SS. The notation ‘a’ and ‘b’ refers to the relative strand orientations. Yellow is for syn and blue is for anti glycosidic bond orientations. The channel cation (K+) is not shown.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

Figure 2: Six two-quartet models were investigated in this work: (a) SA-aabb, (b) SA-abab, (c) SA-aaab, (d) AA, (e) AS and (f) 3AA + 1SS. The notation ‘a’ and ‘b’ refers to the relative strand orientations. Yellow is for syn and blue is for anti glycosidic bond orientations. The channel cation (K+) is not shown.
Mentions: The definitive glycosidic bond conformational patterns observed along G-tracts led to our hypothesis that different glycosidic steps have different relative stabilities, and these differences in stability lead to the different glycosidic bond orientation patterns observed in anti-parallel G-quadruplexes. To test this hypothesis, we built up six two-quartet models (Figure 2) and performed explicit solvent molecular dynamics (MD) simulations with modern force field and simulation protocols. The simulation results provide an understanding of the relative free energies of different G-DNA syn/anti patterns and explain the structural polymorphism of particular G-quadruplex sequences.Figure 2.

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