Sequence Context in DNA i-Motifs Can Nurture Very Stable and Persistent Kinetic Traps

I-motifs are non-canonical DNA structures with recognized biological significance and a proven utility in material engineering. Consequently, understanding and control of i-motif properties is essential to sustain progress across both disciplines. In this work, we systematically investigate how proximity to the most common form of DNA, a double-stranded duplex, influences the thermodynamic and kinetic properties of adjacent i-motifs. We demonstrate that double-stranded stems in i-motif loops promote kinetic trapping of very stable and persistent partially folded conformations. Further, we investigate pathways toward rational control over a folding topology makeup.