Brownian dynamics simulations of single-stranded DNA hairpins

We present a Brownian dynamics model which we use to study the kinetics and thermodynamics of single-stranded DNA hairpins, gaining insights into the role of stem mismatches and the kinetics rates underlying the melting transition. The model is a base-backbone type in which the DNA bases and sugar-phosphate backbone are represented as single units (beads) in the context of the Brownian dynamics simulations. We employ a minimal number of bead-bead interactions, leading to a simple computational scheme. To demonstrate the veracity of our model for DNA hairpins, we show that the model correctly captures the effects of base stacking, hydrogen bonding, and temperature on both the thermodynamics and the kinetics of hairpin formation and melting. When cast in dimensionless form, the thermodynamic results obtained from the present model compare favorably with default predictions of the m -fold server, although the present model is not sufficiently robust to provide dimensional results. The kinetic data at low temperatures indicate frequent but short-lived opening events, consistent with the measured chain end-to-end probability distribution. The model is also used to study the effect of base mismatches in the stem of the hairpin. With the parameters used here, the model overpredicts the relative shift in the melting temperature due to mismatches. The melting transition can be primarily attributed to a rapid increase in the hairpin opening rate rather than an equivalent decrease in the closing rate, in agreement with single-molecule experimental data.