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

Abstract

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.