B‐DNA structure and stability: the role of nucleotide composition and order

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 eff…