title: Explaining the varied glycosidic conformational, G-tract length and sequence preferences for anti-parallel G-quadruplexes.
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.
authors.affiliation: Department of Medicinal Chemistry, College of Pharmacy, University of Utah, Salt Lake City, Utah, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Cang
authors.forename: Jiří
authors.initials: J
authors.lastname: Šponer
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Cheatham
mesh_terms: D001483:Base Sequence; D002236:Carbohydrate Conformation; D019277:Entropy; D054856:G-Quadruplexes; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016615:Telomere / Q000737:chemistry