Hybridization Pathways and Mechanisms of Model DNA Oligonucleotides in Solution.

We propose a coarse-grained lattice model of short DNA strands to investigate the microscopic pathways and mechanisms of oligonucleoides hybridization in solution. The extent to which hybridization in solution conforms to two-state thermodynamics is also analyzed. Monte Carlo simulations with parallel tempering are performed to estimate the equilibrium population of single- and double-stranded states and the associated free-energy landscapes. Sequence complexity is shown to largely dominate the nucleation and helix propagation pathways. The two-state nature of the transition is found to exhibit strong sequence dependence. Although the model predictions are consistent with classical cooperativity signatures, stable intermediates appear, in violation of the two-state assumption.