title: Loop-length-dependent folding of G-quadruplexes.
abstract: Guanine-rich DNA sequences can form a large number of structurally diverse quadruplexes. These vary in terms of strand polarity, loop composition, and conformation. We have derived guidelines for understanding the influence of loop length on the structure adopted by intramolecular quadruplex-forming sequences, using a combination of experimental (using CD and UV melting data) and molecular modeling and simulation techniques. We find that a parallel-stranded intramolecular quadruplex structure is the only possible fold when three single residue loops are present. When single thymine loops are present in combination with longer length loops, or when all loops are longer than two residues, both parallel- and antiparallel-folded structures are able to form. Multiple conformations of each structure are likely to coexist in solution, as they were calculated to have very similar free energies.
authors.affiliation: Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
authors.forename: Pascale
authors.initials: P
authors.lastname: Hazel
authors.forename: Julian
authors.initials: J
authors.lastname: Huppert
authors.forename: Shankar
authors.initials: S
authors.lastname: Balasubramanian
authors.forename: Stephen
authors.initials: S
authors.lastname: Neidle
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry*; D011071:Poly T / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013816:Thermodynamics
chemical_list: D009841:Oligonucleotides; D011071:Poly T; D006147:Guanine; D004247:DNA