Calculation of Hydrodynamic Properties for G-Quadruplex Nucleic Acid Structures from in silico Bead Models
| Autor: | Robert Buscaglia, John O. Trent, Huy T. Le, William L. Dean, Jonathan B. Chaires |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Base Sequence Molecular model Drug discovery Chemistry In silico Context (language use) Computational biology G-quadruplex Molecular biology Small molecule Article G-Quadruplexes Folding (chemistry) Nucleic Acids Drug Discovery Hydrodynamics Nucleic acid Animals Humans heterocyclic compounds |
| Zdroj: | Topics in Current Chemistry ISBN: 9783642347429 |
| Popis: | 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 multiple 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. |
| Databáze: | OpenAIRE |
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