Figure 1.

(A,B): Diagram and oxDNA visualization showing non-interaction/interaction state of the target and gene. (A) A diagram showing the non-interaction/interaction states. $d_{ex}$ and $d_{lig}$ respectively represent the distances between the extension arm and its complementary region on the target gene and the ligation arm and its complementary region on the target gene. These two parameters are respectively represented by $Q_{ex}$ and $Q_{lig}.$ (B) Non-interaction/interaction states of the target and the probe visualized by cogli1, a tool to draw oxDNA configurations. The figure on the left shows a complete open state of the target (colored in red) and the probe (colored in green) in which both $Q_{lig}$ and $Q_{ex}$ equal 10. The figure on the right demonstrates an interaction state of the target and probe where both $Q_{lig}$ and $Q_{ex}$ equal zero. Each visualized nucleotide includes two beads, one representing the backbone and the other the base. There are two interaction sites on the base, including a stacking site as well as a hydrogen-bonding site [11]. (C,D): Free energy calculation for the E. coli gene nemR and molecular inversion probe (MIP). (C) An unbiased sampling frequency distribution over the whole space where $Q_{ex}$ and $Q_{lig}$ range from 0 to 10. (D) The free energy profile along the diagonal plane of part C (marked by the red line). The value of the free energy reflects the change in distance along the diagonal of part C, where $Q_{ex}=Q_{lig}$. The biased sampling frequency and the calculated free energy profile are shown. $\Delta G_{int}$, the free energy of probe–target interaction is labeled in the figure.