Anatomy of Base Pairing in DNA by Interacting Quantum Atoms

Abstract

The formation of purine and pyrimidine base pairs (BPs), which contributes to shaping of the canonical and noncanonical 3D structures of nucleic acids, is one the most investigated phenomena in chemistry and life sciences. In this contribution, the anatomy of the bond energy (BDE) of the base-pairing interaction in 39 different arrangements found experimentally or predicted for DNA structures containing the four common nucleobases (A, C, G, T) in their neutral or protonated forms is described in light of the theory of interacting quantum atoms within the context of the quantum theory of atoms in molecules. The interplay of individual energy components involved in the three stages of the bond formation process (structural deformation, electron-density promotion, and intermolecular interaction) is studied. We recognized that for the neutral BPs, variations in the kinetic and electrostatic contributions to the BDE are rather negligible, leaving the exchange–correlation energy as the main stabilizing component. It is shown that the contribution of the exchange–correlation term can be recovered by including atoms that are formally assumed to be hydrogen bonded (primary interaction). In contrast, to recover the electrostatic component of interaction, one must consider both the primary and secondary (formally nonbonded atoms) interatomic interactions. The results of our study were employed to design new types of BPs with altered bonding anatomy. We demonstrate that improving the electrostatic characteristics of the BPs does not necessarily result in greater interaction energies if weak secondary hydrogen bonding is destroyed. However, the main tuning factor for systems with conserved interacting faces (primary interactions) is the electrostatic component of the interaction energy resulting from the secondary atom–atom electrostatics.

Proton leap: shuttling of protons onto benzonitrile

“…It has been demonstrated that M06-2X functional successfully describes charged particles, 36,49,50 but also systems with various types of interactions. 31,39,51–57 IQA analysis was performed with the AIMAll software 58 by employing the promega5 basin integration method.…”

“…which enables analogous description of the fragment–fragment interaction:Herein, we will use optimized fragments as a reference, according to a recent publication on IQA treatment of DNA base pairs. 39 Energy needed to distort optimized fragments into a geometry they adopt in the complex represents deformation energy E def , whereas promotion energy E pro stands for fragment's (de)stabilization energy in the presence of other fragments. Thus we arrive at the final expression for the IQA binding energy:…”

“…Note that Cuyacot et al 39 analyzed systems composed of two fragments and thus the promotion energy was included in the definition of the interaction energy. In this contribution we investigate interaction of two fragments (BN–PCH + , BN–H + , PC–H + ) and three fragments (BN–H + –PC).…”

“…For this purpose, the Interacting Quantum Atoms methodology 21,22 (IQA) was employed, which has so far been successfully utilized for analysis of diverse systems, properties and processes. 23–41 It enables quantification of classical and non-classical interaction terms among selected fragments (the fragments being BN & PCH + , BN & H + , PC & H + , or BN & H + & PC), but also energetical properties of the fragments themselves when their geometry and the environment modify upon reaction advancement. The paper is organized as follows: Section 2 contains details of the computational procedure; the results and their discussion are presented in Section 3; the conclusions are summarized in Section 4.…”

Classical Electrostatics Remains the Driving Force for Interanion Hydrogen and Halogen Bonding

“…As an iconic concept in chemistry and an illuminating reference for the development of novel noncovalent interactions, hydrogen bonding (HB) is ubiquitous and plays an essential role in chemistry, biology, and material sciences. − For the sake of convenience, HB is usually denoted as A···H-D, where H-D stands for the hydrogen donor with an electrophilic hydrogen atom and D is an electronegative atom or group and A is an electron-rich center, which is negatively charged and thus serves as the hydrogen acceptor. The current consensus is that electrostatic attraction between H and A governs HB. , Certain energy analyses show that the attractive electrostatic interaction benefits from a comparable contribution from the quantum exchange-correlation energy component . Meanwhile, the minor charge transfer (CT) interaction, or n A → σ* H‑D , stabilizes HB as well and is responsible for the covalent features such as the directionality in HB. − Due to the dominance of electrostatics, electrostatic concepts, such as atomic charges, multipoles, and polarizability, have been successfully adopted in the force field description of HB. − Recently, the scope of HB has been noticeably expanded with various unconventional cases identified. − Among these unconventional HBs, interanion HB (IAHB) − is particularly intriguing as it seemingly violates the long-standing electrostatic explanation and thus challenges the force field description, as Coulombic repulsion would prevent the formation of such HB.…”