  We study the dynamics of DNA hairpin formation using oxDNA, a
nucleotide-level coarse-grained model of DNA. In particular, we explore the
effects of the loop stacking interactions and non-native base pairing on the
hairpin closing times. We find a non-monotonic variation of the hairpin closing
time with temperature, in agreement with the experimental work of Wallace et
al. [Proc. Nat. Acad. Sci. USA 2001, 98, 5584-5589]. The hairpin closing
process involves the formation of an initial nucleus of one or two bonds
between the stems followed by a rapid zippering of the stem. At high
temperatures, typically above the hairpin melting temperature, an effective
negative activation enthalpy is observed because the nucleus has a lower
enthalpy than the open state. By contrast, at low temperatures, the activation
enthalpy becomes positive mainly due to the increasing energetic cost of
bending a loop that becomes increasingly highly stacked as the temperature
decreases. We show that stacking must be very strong to induce this
experimentally observed behavior, and that the existence of just a few weak
stacking points along the loop can substantially suppress it. Non-native base
pairs are observed to have only a small effect, slightly accelerating hairpin
formation.
