Energy Landscapes and Hybridization Pathways for DNA Hexamer Duplexes

Strand hybridization is not only a fundamental molecular mechanism underlying the biological functions of nucleic acids but is also a key step in the design of efficient nanodevices. Despite recent efforts, the microscopic rules governing the hybridization mechanisms remain largely unknown. In this study, we exploit the energy landscape framework to assess how sequence-specificity modulates the hybridization mechanisms in DNA. We find that GG-tracts hybridize much more rapidly compared to GC-tracts, via either zippering or slithering pathways. For the hybridization of GG-tracts, both zippering and slithering mechanisms appear to be kinetically relevant. In contrast, for the GC-tracts, the zippering mechanism is dominant. Our work reveals that even for the relatively small systems considered, the energy landscapes feature multiple metastable states and kinetic traps, which is at odds with the conventional “all-or-nothing” model of DNA hybridization formulated on the basis of thermodynamic arguments alone. Interestingly, entropic effects are found to play an important role in determining the thermal stability of competing conformational ensembles and in determining the preferred hybridization pathways.