Quantum Mechanical Investigation of the G-Quadruplex Systems of Human Telomere

[Image: see text] The three G-quadruplexes involved in the human telomere have been studied with an accurate quantum mechanical approach, and the possibility of reducing them to a simpler model has been tested. The similarities and the differences of these three systems are shown and discussed. Each system has been analyzed through different properties and compared to the others. In particular, we have considered: (1) the shape of the cavity and the atomic charges around it; (2) the electric field in and out of the cavity; (3) the stabilization energy due to the stacking of G-tetrads, to the H-bonds and to the ion interactions; and, finally, (4) to study the mechanism of the process of the ion inclusion in the cavity, the curves of potential energy due to the movement of the Na(+) and K(+) ions toward the cavity. The results suggest that a detailed study is essential in order to obtain the quantitative properties of these complex systems, but also that some qualitative behaviors can be schematized. Our study makes it clear that the entry of an ion in the cavity of these systems is a complex process, where it is possible to find stable structures with the ion out and in the cavity. Moreover, it is possible that more than one diabatic state is involved in this process.