Calculation of hydrodynamic properties for G-quadruplex nucleic acid structures from in silico bead models

Huy T. Le, Robert Buscaglia, William L. Dean, Jonathan B. Chaires, John O. Trent

Research output: Chapter in Book/Report/Conference proceedingChapter

16 Scopus citations


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.

Original languageEnglish (US)
Title of host publicationQuadruplex Nucleic Acids
EditorsJonathan B. Chaires, David Graves
Number of pages32
StatePublished - 2013
Externally publishedYes

Publication series

NameTopics in Current Chemistry
ISSN (Print)0340-1022


  • Bead models
  • Drug discovery
  • G-quadruplex
  • Hydrodynamic
  • Nucleic acids
  • Sedimentation

ASJC Scopus subject areas

  • General Chemistry


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