An atlas of RNA base pairs involving modified nucleobases with optimal geometries and accurate energies

Abstract

Posttranscriptional modifications greatly enhance the chemical information of RNA molecules, contributing to explain the diversity of their structures and functions. A significant fraction of RNA experimental structures available to date present modified nucleobases, with half of them being involved in H-bonding interactions with other bases, i.e. ‘modified base pairs’. Herein we present a systematic investigation of modified base pairs, in the context of experimental RNA structures. To this end, we first compiled an atlas of experimentally observed modified base pairs, for which we recorded occurrences and structural context. Then, for each base pair, we selected a representative for subsequent quantum mechanics calculations, to find out its optimal geometry and interaction energy. Our structural analyses show that most of the modified base pairs are non Watson–Crick like and are involved in RNA tertiary structure motifs. In addition, quantum mechanics calculations quantify and provide a rationale for the impact of the different modifications on the geometry and stability of the base pairs they participate in.

Theoretical characterization of sulfur-to-selenium substitution in an emissive RNA alphabet: impact on H-bonding potential and photophysical properties

“…This is the standard approach used in literature. 36,37,40,[42][43][44][45][46][47] 2.2 Electronic structure calculations. The geometry optimizations of the H-bonded base pairs were performed utilizing a DFT approach, based on the hybrid B3LYP functional as implemented in the Gaussian09 package.…”

Highly accurate equilibrium structure of the C2h symmetric N1‐to‐O2 hydrogen‐bonded uracil‐dimer

“…Nucleobases are quintessential components of life and their structures and molecular complexes are of high interest for both the experimental and computational community. Interaction energies for intermolecular (model) complexes, that is, stacking of bases or hydrogen‐bonded complexes, have been thoroughly investigated over the last decade with a multitude of different computational methods . For many of these model complexes the interaction energies are reliably known up to tenths of kcal·mol −1 accuracy and beyond.…”

“…Interaction energies for intermolecular (model) complexes, that is, stacking of bases or hydrogen-bonded complexes, have been thoroughly investigated over the last decade with a multitude of different computational methods. [1][2][3] For many of these model complexes the interaction energies are reliably known up to tenths of kcalÁmol 21 accuracy and beyond. However, essentially all these studies necessarily rely on a lower level of theory to obtain the complex geometry.…”

Chemical and Conformational Diversity of Modified Nucleosides Affects tRNA Structure and Function

“…As discussed, the modifications of the tRNA core contribute to the tertiary folding of tRNA into the canonical and functioning three-dimensional shape. For the most part, modifications in the core, methylations in particular, negate Watson-Crick base pairing resulting in a three-dimensional structure with non-canonical base pairs and base triples of varying stability [236,237]. The modifications of the anticodon stem and loop enable some 40 tRNAs to read the 61 amino acid codons, and yet retain a common conformation and dynamic acceptable to translation.…”