Energy Landscapes of Mini-Dumbbell DNA Octanucleotides

Single-stranded DNA structures play a significant role in biological systems, in particular during replication, translation, and DNA repair. Tracts of simple repetitive DNA are associated with slipped-strand mispairing, which can lead to genetic diseases. Recent NMR studies of TTTA and CCTG repeats have shown that these sequences form mini-dumbbells (MDBs), leading to frameshift mutations. Here we explore the energy landscapes of (CCTG)₂ and (TTTA)₂, which are currently the smallest known molecules to form MDBs. While (CCTG)₂ MDBs are stable, (TTTA)₂ exhibits numerous other structures with lower energies. A key factor identified in the stabilization of MDB structures is the bonding strength between residues 1 and 4, and 5 and 8.