What sustains the unnatural base pairs (UBPs) with no hydrogen bonds

The recent report of a hydrophobic unnatural base pair (UBP), d5SICS-dNaM, which replicated in DNA PCR and also sustained and synthesized a plasmid inside E. coli genome by Romesberg and coworkers, is intriguing. Quantum chemical calculations show that the UBPs prefer a slipped parallel configuration to facilitate weak dispersion interactions somewhat similar to the so-called π-stacking interaction. Nevertheless, within a natural DNA tract, classical molecular dynamics simulations show that the backbone and neighboring stacked bases together reorient the UBPs in natural base pair like planar environment. Our computed structure with an average end-end distance, dC1'-C1' = 10.7 Å for d5SICS-dNaM is in excellent agreement with available crystal structure (PDB ID: 3SV3 , planar UBP with dC1'-C1'(crystal) = 11.0 Å). Quantum mechanical calculations for the UBP flanked by two natural base-pairs (A-T) on top and on bottom on equilibrated MD structure found large binding energy (ΔE = -74.0 kcal/mol). The present calculations therefore establish the fact that the hydrophobic UBPs can be stabilized by dispersion interactions with other base pairs in the DNA tract even in the absence of any hydrogen bonding between the UBPs themselves.