A Coarse-Grained Model of Unstructured Single-Stranded DNA Derived from Atomistic Simulation and Single-Molecule Experiment.

Abstract

A simple coarse-grained model of single-stranded DNA (ssDNA) was developed, 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 nonbonded 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 2 orders of magnitude of the applied force. The accuracy of the model was confirmed by 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.