title: Calculation of hydrodynamic properties for G-quadruplex nucleic acid structures from in silico bead models.
abstract: Nucleic acids enriched in guanine bases can adopt unique quadruple helical tertiary structures known as G-quadruplexes. G-quadruplexes have emerged as attractive drug targets as many G-quadruplex-forming sequences have been discovered in functionally critical sites within the human genome, including the telomere, oncogene promoters, and mRNA processing sites. A single G-quadruplex-forming sequence can adopt one of many folding topologies, often resulting in a lack of a single definitive atomic-level resolution structure for many of these sequences and a major challenge to the discovery of G-quadruplex-selective small molecule drugs. Low-resolution techniques employed to study G-quadruplex structures (e.g., CD spectroscopy) are often unable to discern between G-quadruplex structural ensembles, while high-resolution techniques (e.g., NMR spectroscopy) can be overwhelmed by a highly polymorphic system. Hydrodynamic bead modeling is an approach to studying G-quadruplex structures that could bridge the gap between low-resolution techniques and high-resolution molecular models. Here, we present a discussion of hydrodynamic bead modeling in the context of studying G-quadruplex structures, highlighting recent successes and limitations to this approach, as well as an example featuring a G-quadruplex structure formed from the human telomere. This example can easily be adapted to the investigation of any other G-quadruplex-forming sequences.
authors.affiliation: Clinical and Translation Research Building, University of Louisville, 505 S. Hancock St, Louisville, KY, 40202, USA.
authors.forename: Huy T
authors.initials: HT
authors.lastname: Le
authors.forename: Robert
authors.initials: R
authors.lastname: Buscaglia
authors.forename: William L
authors.initials: WL
authors.lastname: Dean
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Chaires
authors.forename: John O
authors.initials: JO
authors.lastname: Trent
mesh_terms: D000818:Animals; D001483:Base Sequence; D055808:Drug Discovery; D054856:G-Quadruplexes; D006801:Humans; D057446:Hydrodynamics; D008958:Models, Molecular; D009696:Nucleic Acids / Q000737:chemistry*
chemical_list: D009696:Nucleic Acids