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

ChemistryOpen

Dr. Trevor A. Hamlin¹  Celine Nieuwland¹  Prof. Dr. F. Matthias Bickelhaupt¹  Prof. Dr. Célia Fonseca Guerra¹  Prof. Dr. Giampaolo Barone² 

[1]Department of Theoretical Chemistry Amsterdam Institute of Molecular and Life Sciences (AIMMS) Amsterdam Center for Multiscale Modeling (ACMM) Vrije Universiteit Amsterdam De Boelelaan 1083 1081 HV Amsterdam (The Netherlands

[2]Dipartimento di Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche Università degli Studi di Palermo Viale delle Scienze, Edificio 17 90128 Palermo Italy

关键词: activation strain model;    density functional calculations;    diagonal interactions;    DNA structures;    nucleotide composition;   

DOI  :  10.1002/open.202100231

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown