Formation Pathways of a Guanine-Quadruplex DNA Revealed by Molecular Dynamics and Thermodynamics Analysis of the Substates

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Publikace nespadá pod Pedagogickou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
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ŠTEFL Richard CHEATHAM Thomas E. ŠPAČKOVÁ Naděžda FADRNÁ Eva BERGER Imre KOČA Jaroslav ŠPONER Jiří

Rok publikování 2003
Druh Článek v odborném periodiku
Časopis / Zdroj Biophysical Journal
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www http://www.biophysj.org
Obor Fyzikální chemie a teoretická chemie
Klíčová slova G-DNA;quadruplex;molecular dynamics
Popis The formation of a cation-stabilized guanine quadruplex (G-DNA) stem is an exceptionally slow process involving complex kinetics that has not yet been characterized at atomic resolution. Here, we investigate the formation of a parallel stranded G-DNA stem consisting of four strands of d(GGGG) using molecular dynamics simulations with explicit inclusion of counterions and solvent. Due to the limitations imposed by the nanosecond timescale of the simulations, rather than watching for the spontaneous formation of G-DNA, our approach probes the stability of possible supramolecular intermediates (including two-, three-, and four-stranded assemblies with out-of-register basepairing between guanines) on the formation pathway. The simulations suggest that "cross-like" two-stranded assemblies may serve as nucleation centers in the initial formation of parallel stranded G-DNA quadruplexes, proceeding through a series of rearrangements involving trapping of cations, association of additional strands, and progressive slippage of strands toward the full stem. To supplement the analysis, approximate free energies of the models are obtained with explicit consideration of the integral cations. The approach applied here serves as a prototype for qualitatively investigating other G-DNA molecules using molecular dynamics simulation and free-energy analysis.
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