RNA versus DNA G‐Quadruplex: The Origin of Increased Stability

• Published in: Chemistry : a European journal Vol. 24; no. 61; pp. 16315 - 16322
• Main Authors: Zaccaria, Francesco, Fonseca Guerra, Célia
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 02.11.2018; John Wiley and Sons Inc
• Subjects: Alkali metals; Aqueous environments; bonding analysis; Cations; Cations - chemistry; Chemistry; Computer simulation; density functional calculations; Density functional theory; Deoxyribonucleic acid; DNA; DNA - chemistry; DNA structures; Electrostatic properties; Electrostatics; G-Quadruplexes; Hydrogen Bonding; Metal ions; Metals, Alkali - chemistry; Models, Molecular; noncovalent interactions; Nucleic Acid Conformation; Organic chemistry; Oxygen atoms; quadruplex; Quantum chemistry; Ribonucleic acid; RNA; RNA - chemistry; RNS structures; Static Electricity; Thermodynamics; density functional calculations; quadruplex; bonding analysis; noncovalent interactions; DNA structures; RNS structures
• ISSN: 0947-6539; 1521-3765; 1521-3765
• DOI: 10.1002/chem.201803530

DNA quadruplexes have been the subject of investigation because of their biological relevance and because of their potential application in supramolecular chemistry. Similarly, RNA quadruplexes are now gaining increasing attention. Although DNA and RNA quadruplexes are structurally very similar, the latter show higher stability. In this study we report dispersion‐corrected density functional theory (DFT‐D) quantum chemical calculations that were undertaken to understand the difference in stabilities of RNA and DNA quadruplexes. The smallest meaningful model of a stack of quartets, interacting with alkali metal cations, was simulated in an aqueous environment. The energy decomposition analysis allows for in‐depth examination of the interaction energies, emphasising the role of noncovalent interactions and better electrostatics in determining RNA‐GQs higher stabilities, particularly pinpointing the role of the extra 2′‐OH groups. Furthermore, our computations present new insights on why the cation is required for self‐assembly: unexpectedly the cation is not necessary to relieve the repulsion between the oxygen atoms in the central cavity, but it is needed to overcome the entropic penalty. Why so stable? Dispersion‐corrected (DFT‐D) quantum chemical calculations on the stabilities of RNA and DNA quadruplexes show electrostatic interactions and hydrogen bonds make the decisive difference (see figure).