Sequence-dependent thermodynamics of a coarse-grained DNA model

TL;DR

This paper develops a sequence-dependent coarse-grained DNA model that accurately predicts melting temperatures and other properties, enhancing the understanding of DNA thermodynamics with a flexible, validated simulation framework.

Contribution

The authors introduce a sequence-dependent parametrization for a coarse-grained DNA model, fitting it to melting temperatures of numerous sequences, and demonstrate its application to various DNA structural and thermodynamic properties.

Findings

Model accurately reproduces melting temperatures across sequences

Good agreement with experimental data on DNA properties

Flexible simulation code available for further research

Abstract

We introduce a sequence-dependent parametrization for a coarse-grained DNA model [T. E. Ouldridge, A. A. Louis, and J. P. K. Doye, J. Chem. Phys. 134, 085101 (2011)] originally designed to reproduce the properties of DNA molecules with average sequences. The new parametrization introduces sequence-dependent stacking and base-pairing interaction strengths chosen to reproduce the melting temperatures of short duplexes. By developing a histogram reweighting technique, we are able to fit our parameters to the melting temperatures of thousands of sequences. To demonstrate the flexibility of the model, we study the effects of sequence on: (a) the heterogeneous stacking transition of single strands, (b) the tendency of a duplex to fray at its melting point, (c) the effects of stacking strength in the loop on the melting temperature of hairpins, (d) the force-extension properties of single strands and (e) the structure of a kissing-loop complex. Where possible we compare our results with experimental data and find a good agreement. A simulation code called oxDNA, implementing our model, is available as free software.