Determining the DNA stability parameters for the breathing dynamics of heterogeneous DNA by stochastic optimization

TL;DR

This paper introduces a stochastic optimization method using simulated annealing to accurately infer DNA stability parameters from bubble breathing dynamics, enabling analysis from single-molecule data rather than equilibrium measurements.

Contribution

It presents a novel approach to determine DNA thermodynamic stability parameters directly from breathing dynamics using stochastic optimization.

Findings

Accurately infers DNA stability parameters from noisy breathing data.

Method works with single-molecule bubble breathing assays.

Provides a new tool for DNA thermodynamics analysis.

Abstract

We suggest that the thermodynamic stability parameters (nearest neighbor stacking and hydrogen bonding free energies) of double-stranded DNA molecules can be inferred reliably from time series of the size fluctuations (breathing) of local denaturation zones (bubbles). On the basis of the reconstructed bubble size distribution, this is achieved through stochastic optimization of the free energies in terms of Simulated Annealing. In particular, it is shown that even noisy time series allow the identification of the stability parameters at remarkable accuracy. This method will be useful to obtain the DNA stacking and hydrogen bonding free energies from single bubble breathing assays rather than equilibrium data.