An Investigation of G-Quadruplex Structural Polymorphism in the Human Telomere Using a Combined Approach of Hydrodynamic Bead Modeling and Molecular Dynamics Simulation
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- 作者：Huy T. Le ; William L. Dean ; Robert Buscaglia ; Jonathan B. Chaires ; John O. Trent
- 刊名：Journal of Physical Chemistry B
- 出版年：2014
- 出版时间：May 22, 2014
- 年：2014
- 卷：118
- 期：20
- 页码：5390-5405
- 全文大小：740K
- 年卷期：v.118,no.20(May 22, 2014)
- ISSN：1520-5207
文摘
Guanine-rich oligonucleotides can adopt noncanonical tertiary structures known as G-quadruplexes, which can exist in different forms depending on experimental conditions. High-resolution structural methods, such as X-ray crystallography and NMR spectroscopy, have been of limited usefulness in resolving the inherent structural polymorphism associated with G-quadruplex formation. The lack of, or the ambiguous nature of, currently available high-resolution structural data, in turn, has severely hindered investigations into the nature of these structures and their interactions with small-molecule inhibitors. We have used molecular dynamics in conjunction with hydrodynamic bead modeling to study the structures of the human telomeric G-quadruplex-forming sequences at the atomic level. We demonstrated that molecular dynamics can reproduce experimental hydrodynamic measurements and thus can be a powerful tool in the structural study of existing G-quadruplex sequences or in the prediction of new G-quadruplex structures.