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.