Coarse-grained model of single-stranded nucleic acids

The Aksimentiev lab developed a simple coarse-grained model of single-stranded DNA (ssDNA), featuring only two sites per nucleotide that represent the centers of mass of the backbone and sugar/base groups.  In the model, the interactions between sites are described using tabulated bonded potentials optimized to reproduce the solution structure of DNA observed in atomistic molecular dynamics simulations.  Isotropic potentials describe non-bonded interactions, implicitly taking into account the solvent conditions to match the experimentally determined radius of gyration of ssDNA.  The model reproduces experimentally measured force-extension dependence of an unstructured DNA strand across two orders of magnitude of the applied force.  The accuracy of the model was confirmed through collaborations with the Ha lab, measuring the end-to-end distance of a dT14 fragment via FRET while stretching the molecules using optical tweezers.  The model offers straightforward generalization to systems containing double-stranded DNA and DNA binding proteins. The article can be viewed at http://pubs.acs.org/doi/full/10.1021/ct500193u