Electronic Energy Changes Associated with Guanine Quadruplex Formation: An Investigation at the Atomic Level

Abstract

Guanine quadruplexes have received a lot of attention due to their possible role as therapeutic agents. Specifically, it is the ability of these quadruplex structures to inhibit telomerase, an enzyme found to be highly active in a large percentage of tumor cells and thought to confer immortality upon these cells. However, although a great deal of research has focused on enhancing the formation of these structures and their anticancer activity, many questions remain about the quadruplex structures themselves. The current study probes the nature of these quadruplex structures at the atomic level. Individual atomic energies have been computed for the quadruplex structure and compared to the atomic energies of the unfolded telomere to determine the energetic consequences of quadruplex formation. The results suggest several interesting trends, most notably that the guanine quartets exhibit an alternating pattern of stabilization and destabilization and these regions actually overlap in the intact quadruplex. In addition, the TTA loop segments are largely stabilized, whereas the atoms in the sugar-phosphate backbone exhibit mostly minor changes going from the unfolded to folded state. Inclusion of additional sodium cations in the central core of the quadruplex has a minimal effect on the atomic energies except for the atoms that are closest to the cations, which are largely stabilized in the presence of these ions.

Cooperativity between hydrogen bonds and beryllium bonds in (H2O)nBeX2 (n = 1–3, X = H, F) complexes. A new perspective

“…A further perspective is available within the framework of QTAIM based on the evaluation of atomic energy components. 61,62 QTAIM defines atoms as open systems bound by zero-flux surfaces, called atomic basins. Integration over these basins yields very accurate atomic information.…”

“…62. It has been demonstrated 61,62 that atomic energies are a useful tool for describing internal energy changes in weakly bound systems. The changes in atomic energies correlate with changing atomic stabilities within the system, thus giving insight into the distribution of the stabilization and destabilization present in the BeX 2 :H 2 O moieties.…”

Von Carbanionen zu metallorganischen Verbindungen: Quantifizierung des Metallionen‐Effekts auf die nucleophile Reaktivität

“…QTAIM defines atomic basins as regions bounded by zero flux surfaces, and the integration over these basins yields very accurate atomic information. In particular, it has been shown that the variation of atomic energies provides reliable information on the stabilization and destabilization of the interacting subunits in weakly bound molecular aggregates,27b,c and can also reflect cooperative effects 14b. d The atomic energy changes for the clusters are calculated with respect to the energy of each atom as it exists in the monomers that form the cluster.…”

Atomic partitioning of M–H2 bonds in [NiFe] hydrogenase – a test case of concurrent binding

“…This method of using atomic energy to understand the local regions of stabilization within biomolecules that are connected through weak interactions like hydrogen bonds is an emerging field of interest. 46,47 Recently, Boyd and his coworkers demonstrated through such methods that the atomic basins of the bridging hydrogens are destabilized in the water clusters due to the cooperativity of hydrogen bonds. 48,49 C. F. Matta et al has used this method for the computation of the vibrationless 0 K electronic bond dissociation energy (BDE) as the sum of atomic contributions, for the P-O bond cleavage reaction in biological systems.…”