B-DNA Structure and Stability: The Role of Nucleotide Composition and Order.

Celine Nieuwland, Trevor A Hamlin, Célia Fonseca Guerra, Giampaolo Barone, F Matthias Bickelhaupt

ChemistryOpen 2022 Feb

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We have quantum chemically analyzed the influence of nucleotide composition and sequence (that is, order) on the stability of double-stranded B-DNA triplets in aqueous solution. To this end, we have investigated the structure and bonding of all 32 possible DNA duplexes with Watson-Crick base pairing, using dispersion-corrected DFT at the BLYP-D3(BJ)/TZ2P level and COSMO for simulating aqueous solvation. We find enhanced stabilities for duplexes possessing a higher GC base pair content. Our activation strain analyses unexpectedly identify the loss of stacking interactions within individual strands as a destabilizing factor in the duplex formation, in addition to the better-known effects of partial desolvation. Furthermore, we show that the sequence-dependent differences in the interaction energy for duplexes of the same overall base pair composition result from the so-called "diagonal interactions" or "cross terms". Whether cross terms are stabilizing or destabilizing depends on the nature of the electrostatic interaction between polar functional groups in the pertinent nucleobases. © 2022 The Authors. Published by Wiley-VCH GmbH.

Citation

Celine Nieuwland, Trevor A Hamlin, Célia Fonseca Guerra, Giampaolo Barone, F Matthias Bickelhaupt. B-DNA Structure and Stability: The Role of Nucleotide Composition and Order. ChemistryOpen. 2022 Feb;11(2):e202100231