To determine the potential for intra-DNA interactions when A3A is bound to a (T/C)TC(A/G) signature sequence, molecular models were developed based on the crystal structures of A3A bound to ssDNA (PDB ID: 5KEG and 5SWW)20,22. These models orient the bases of the −2 and +1 nucleotides so that they form hydrogen bonds at an angle of approximately 120 degrees and distance of less than 3.5 Å, with the larger purine at +1 position stacking on His29 and the smaller −2 pyrimidine coordinating the +1 base (Fig. 5e,f). The reversal of the nucleotides at +1 and −2 positions would not result in a fit nearly as well, which could explain the lower affinity of purine-TC-pyrimidine. Thus the structural model explains the preference for (T/C)TC(A/G) and suggests stabilizing inter-DNA interactions may further increase the affinity.