The corresponding fragment-pairwise LED interaction in gas phase and in water are given in Fig. . The binding energy between the two strands amounts to -179.2 kcal/mol in the gas phase and -80.1 kcal/mol in water (these figures do not consider the repulsion between the negatively charged backbones, which would make the interaction between the strands highly repulsive in the gas phase, as discussed in the SI). These values primarily originate from interactions between fragment pairs on different strands. The contribution from changes in intra-strand interactions upon duplex formation is minimal, summing to only 0.71 kcal/mol in the gas phase and 0.16 kcal/mol in water.