Loop-Length-Dependent Folding of G-Quadruplexes

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.