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The high-energy 3′,5′phosphodiester linkages conservedin 3′,5′ cyclic GMPs offer a genuine solution for monomeractivation required by the transphosphorylation reactions that couldlead to the emergence of the first simple oligonucleotide sequenceson the early Earth. In this work we provide an in-depth characterizationof the effect of the reaction conditions on the yield of the polymerizationreaction of 3′,5′ cyclic GMPs both in aqueous environmentas well as under dehydrating conditions. We show that the thresholdtemperature of the polymerization is about 30 °C lower underdehydrating conditions than in solution. In addition, we present aplausible exergonic reaction pathway for the polymerization reaction,which involves transient formation of anionic centers at the O3′positions of the participating riboses. We suggest that excess Na+cations inhibit the polymerization reaction because theyblock the anionic mechanism via neutralizing the negatively chargedO3′. Our experimental findings are compatible with a prebioticscenario, where gradual desiccation of the environment could inducepolymerization of 3′,5′ cyclic GMPs synthesized in liquid. [ABSTRACT FROM AUTHOR]

In this feature article, we provide a side-by-side introduction for two research fields: quantum chemical calculations of molecular interaction in nucleic acids and RNA structural bioinformatics. Our main aim is to demonstrate that these research areas, while largely separated in contemporary literature, have substantial potential to complement each other that could significantly contribute to our understanding of the exciting world of nucleic acids. We identify research questions amenable to the combined application of modern ab initio methods and bioinformatics analysis of experimental structures while also assessing the limitations of these approaches. The ultimate aim is to attain valuable physicochemical insights regarding the nature of the fundamental molecular interactions and how they shape RNA structures, dynamics, function, and evolution. [ABSTRACT FROM AUTHOR]

Base pairs belonging to the cis Hoogsteen:sugar-edge (H:S) family play important structural roles in folded RNA molecules. Several of these are present in internal loops, where they are involved in interactions leading to planar dinucleotide platforms which stabilize higher order structures such as base triplets and quartets. We report results of analysis of 30 representative examples spanning 16 possible base pair combinations, with several of them showing multimodality of base pairing geometry. The geometries of 23 of these base pairs were modeled directly from coordinates extracted from RNA crystal structures. The other seven were predicted structures which were modeled on the basis of observed isosteric analogues. After appropriate satisfaction of residual valencies, these structures were relaxed using the B3LYP/6-31G(d,p) method and interaction energies were derived at the RIMP2/aug-cc-pVDZ level of theory. The geometries for each of the studied base pairs have been characterized in terms of the number and nature of H-bonds, rmsd values observed on optimization, base pair geometrical parameters, and sugar pucker analysis. In addition to its evaluation, the nature of intermolecular interaction in these complexes was also analyzed using Morokuma decomposition. The gas phase interaction energies range between −5.2 and −20.6 kcal/mol and, in contrast to the H:S trans base pairs, show enhanced relative importance of the electron correlation component, indicative of the greater role of dispersion energy in stabilization of these base pairs. The rich variety of hydrogen bonding pattern, involving the flexible sugar edge, appears to hold the key to several features of structural motifs, such as planarity and propensity to participate in triplets, observed in this family of base pairs. This work explores these aspects by integrating database analysis, and detailed base pairing geometry analysis at the atomistic level, with ab initio computation of interaction energies. The study, involving alternative classification of base pairs and triplets, provides insights into intrinsic properties of these base pairs and their possible structural and functional roles. [ABSTRACT FROM AUTHOR]

The RNA kink-turn is an important recurrent RNA motif, an internal loop with characteristic consensus sequence forming highly conserved three-dimensional structure. Functional arrangement of RNA kink-turns shows a sharp bend in the phosphodiester backbone. Among other signature interactions, kink-turns form A-minor interaction between their two stems. Most kink-turns possess extended A-minor I (A-I) interaction where adenine of the second A•G base pair of the NC-stem interacts with the first canonical pair of the C-stem (i.e., the receptor pair) via trans-sugar-edge/sugar-edge (tSS) and cis-sugar-edge/sugar-edge (cSS) interactions. The remaining kink-turns have less compact A-minor 0 (A-0) interaction with just one tSS contact. We show that kink-turns with A-I in ribosomal X-ray structures keep G═C receptor base pair during evolution while the inverted pair (C═G) is not realized. In contrast, kink-turns with A-0 in the observed structures alternate G═C and C═G base pairs in sequences. We carried out an extended set (~5 μs) of explicit-solvent molecular dynamics simulations of kink-turns to rationalize this structural/evolutionary pattern. The simulations were done using a net-neutral Na(+) cation atmosphere (with ~0.25 M cation concentration) supplemented by simulations with either excess salt KCl atmosphere or inclusion of Mg(2+). The results do not seem to depend on the treatment of ions. The simulations started with X-ray structures of several kink-turns while we tested the response of the simulated system to base substitutions, modest structural perturbations and constraints. The trends seen in the simulations reveal that the A-I/G═C arrangement is preferred over all three other structures. The A-I/C═G triple appears structurally entirely unstable, consistent with the covariation patterns seen during the evolution. The A-0 arrangements tend to shift toward the A-I pattern in simulations, which suggests that formation of the A-0 interaction is likely supported by the surrounding protein and RNA molecules. A-0 may also be stabilized by additional kink-turn nucleotides not belonging to the kink-turn consensus, as shown for the kink-turn from ribosomal Helix 15. Quantum-chemical calculations on all four A-minor triples suggest that there is a different balance of electrostatic and dispersion stabilization in the A-I/G═C and A-I/C═G triples, which may explain different behavior of these otherwise isosteric triples in the context of kink-turns., (© 2011 American Chemical Society)