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| DNA molecules are highly charged semi-flexible polymers that are involved in a wide variety of highly dynamical processes such transcription, replication and packing into organized structures that have different degrees of compaction. Characterizing the free energy landscape around DNA molecules is essential to understanding the energetics and kinetics of such processes. We developed a novel three-dimensional umbrella sampling technique for computing the potential of mean force for ligands interacting with DNA. Using this approach we performed molecular dynamics simulations to quantitatively elucidate the thermodynamic basis for 1D-sliding motions of small charge ligands along the DNAs minor groove. We also determined the three-dimensional potential of mean force (3D-PMF) for a Na+ cation and for the arginine analog methyl guanidinium. The computed PMFs show that, even for small ligands, the free energy landscapes are far from smooth. |
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