Sequence Effects in the Renaturation of DNA Oligonucleotides: Mechanistic Details and Structure

DNA hybridization plays a central role in biology and, increasingly, in materials science. Yet, there is no precedent for examining the pathways by which specific single stranded DNA sequences interact to assemble into a double helix. A detailed model of DNA is adopted in this work to examine such pathways, and to determine the role of sequence, if any, on DNA hybridization. Free-energy methods are used to extract denaturation profiles and thermodynamic quantities, while transition path sampling (TPS) and forward flux sampling (FFS) calculations are used to extract mechanistic and kinetic details about the renaturation reaction. Results reveal that DNA rehybridization is prompted by a distinct nucleation event involving molecular sites with approximately four bases pairing with partners slightly offset from those involved in ideal duplexation. Nucleation is promoted in regions with repetitive base-pair sequence motifs, which yield multiple possibilities for finding complementary base partners. Repetitive sequences follow a nonspecific pathway to renaturation consistent with a molecular “slithering” mechanism, whereas random sequences favor a restrictive pathway involving the formation of key base-pairs before renaturation fully ensues.