Theoretical studies on the folding mechanisms for different DNA G-quadruplexes.
The G-quadruplex DNA formed by the stack of guanines in human telomere sequence is a promising anticancer target. In this study we used the energy landscape theory to elucidate the folding mechanisms for the thrombin aptamer, Form 1 and Form 3 G-quadruplexes. The three G-quadruplexes were simulated with all-atom Gō-model. Results show that, the three G-quadruplexes fold through a two-state mechanism. In the initial stage of the folding process, the compact structures are formed. The G-quadruplexes need to form G-triplex structures on the basis of the compact structures before folding to the native states. The folding free energy barrier of Form 3 G-quadruplex is higher than thrombin aptamer and Form 1, which shows that the structure of Form 3 G-quadruplex has more stability than the other two G-quadruplexes.
Laboratory of Molecular Modeling and Design, State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Science, Dalian, Liaoning, China.
Xue
X
Wu
Peijun
P
Xu
Jinguang
J
Wang
Yong
Y
Xu
Ting
T
Fu
Meixia
M
Zhao
Depeng
D
Zhang
Jiahui
J
Liu
Hujun
H
Shen
Zhilong
Z
Xiu
Guohui
G
Li
D054856:G-Quadruplexes; D009690:Nucleic Acid Conformation