title: The role of loop stacking in the dynamics of DNA hairpin formation.
abstract: 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 nonmonotonic variation of the hairpin closing time with temperature, in agreement with the experimental work of Wallace et al. (Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 5584-5589). The hairpin closing process involves the formation of an initial nucleus of one or two bonds in the stem 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.
authors.affiliation: Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford , South Parks Road, Oxford OX1 3QZ, United Kingdom.
authors.forename: Majid
authors.initials: M
authors.lastname: Mosayebi
authors.forename: Flavio
authors.initials: F
authors.lastname: Romano
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Ouldridge
authors.forename: Ard A
authors.initials: AA
authors.lastname: Louis
authors.forename: Jonathan P K
authors.initials: JP
authors.lastname: Doye
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
chemical_list: D004247:DNA