Polymeric Properties of Telomeric G-Quadruplex Multimers: Effects of Chemically Inert Crowders

G-quadruplexes are noncanonical DNA structures rather ubiquitous in the human genome, which are thought to play a crucial role in the development of the majority of cancers. Here, we present a novel coarse-grained approach in modeling G-quadruplexes that accounts for their structural flexibility. We apply it to study the polymeric properties of G-quadruplex multimers, with and without crowder molecules, to mimic in vivo conditions. We find that, contrary to some suggestions found in the literature, long G-quadruplex multimers are rather flexible polymeric macromolecules, with a local persistence length comparable to monomer size, exhibiting a chain stiffness variation profile consistent with a real polymer in good solvent. Moreover, in a crowded environment (up to 10% volume fraction), we report that G-quadruplex multimers exhibit an increased propensity for coiling, with a corresponding decrease in the measured chain stiffness.