An investigation of G-quadruplex structural polymorphism in the human telomere using a combined approach of hydrodynamic bead modeling and molecular dynamics simulation.
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.
Department of Biochemistry and Molecular Biology, School of Medicine, University of Louisville , HSC-A Building, Room 616, Louisville, Kentucky 40202, United States.
Huy T
HT
Le
William L
WL
Dean
Robert
R
Buscaglia
Jonathan B
JB
Chaires
John O
JO
Trent
D001483:Base Sequence; D016000:Cluster Analysis; D018360:Crystallography, X-Ray; D054856:G-Quadruplexes; D006801:Humans; D057446:Hydrodynamics; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011110:Polymorphism, Genetic; D025341:Principal Component Analysis; D016615:Telomere / Q000235:genetics*; D013816:Thermodynamics; D014461:Ultracentrifugation