Calculation of DNA hybridization energies and misbinding. The DNA hybridization free energy, ΔG is calculated using the nearest neighbor model established by SantaLucia Jr and colleagues, which provides experimental thermodynamic parameters for ΔH37°C and ΔS37°C of correct WC base-pairing, single, double and terminal mismatches, and dangling-ends. These quantities can be used to calculate ΔG at the various temperatures used in our study, ΔG(T) = ΔH37° -TΔS37°C, as it's widely-accepted that ΔH and ΔS are largely independent of temperature for DNA (see Supporting Information, Section S3, for more details). We note that ΔG for two sequences with numerous mismatched base pairs, even in its most energetically favorable alignment can lead to ΔG > 0, meaning -ε'' or -ε' can be greater than 0. In this case, the corresponding misbinding, ε'/ε and ε''/ε are assumed to be 0 since thermodynamically unfavorable binding would not result in attractive misbinding.