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Intrinsic Stacking Interactions of Natural and Artificial Nucleobases

preprint
submitted on 18.12.2019 and posted on 23.12.2019 by Drew P. Harding, Laura J. Kingsley, Glen Spraggon, Steven Wheeler
The intrinsic (gas-phase) stacking energies of natural and artificial nucleobases were explored using density functional theory (DFT) and correlated ab initio methods. Ranking the stacking strength of natural nucleobase dimers revealed a preference in binding partner similar to that seen from experiments, namely G > C > A > T > U. Decomposition of these interaction energies using symmetry-adapted perturbation theory (SAPT) showed that these dispersion dominated interactions are modulated by electrostatics. Artificial nucleobases showed a similar stacking preference for natural nucleobases and were also modulated by electrostatic interactions. A robust predictive multivariate model was developed that quantitively predicts the maximum stacking interaction between natural and a wide range of artificial nucleobases using molecular descriptors based on computed electrostatic potentials (ESPs) and the number of heavy atoms. This model should find utility in designing artificial nucleobase analogs that exhibit stacking interactions comparable to those of natural nucleobases. Further analysis of the descriptors in this model unveil the origin of superior stacking abilities of certain nucleobases, including cytosine and guanine.

Funding

NSF CHE-1807328

History

Email Address of Submitting Author

swheele2@uga.edu

Institution

University of Georgia

Country

USA

ORCID For Submitting Author

0000-0001-7824-6906

Declaration of Conflict of Interest

No conflict of interest.

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