@article {273,
	title = {Molecular mechanism of DNA association with single-stranded DNA binding protein},
	journal = {Nucleic Acids Research},
	volume = {45},
	year = {2017},
	month = {12/2017},
	pages = {12125{\textendash}12139},
	chapter = {12125},
	abstract = {<p>During DNA replication, the single-stranded DNA binding protein (SSB) wraps single-stranded DNA (ssDNA) with high affinity to protect it from degradation and prevent secondary structure formation. Although SSB binds ssDNA tightly, it can be repositioned along ssDNA to follow the advancement of the replication fork. Using all-atom molecular dynamics simulations, we characterized the molecular mechanism of ssDNA association with SSB. Placed in solution, ssDNA{\textendash}SSB assemblies were observed to change their structure spontaneously; such structural changes were suppressed in the crystallographic environment. Repeat simulations of the SSB{\textendash}ssDNA complex under mechanical tension revealed a multitude of possible pathways for ssDNA to come off SSB punctuated by prolonged arrests at reproducible sites at the SSB surface. Ensemble simulations of spontaneous association of short ssDNA fragments with SSB detailed a three-dimensional map of local affinity to DNA; the equilibrium amount of ssDNA bound to SSB was found to depend on the electrolyte concentration but not on the presence of the acidic tips of the SSB tails. Spontaneous formation of ssDNA bulges and their diffusive motion along SSB surface was directly observed in multiple 10-{\textmu}s-long simulations. Such reptation-like motion was confined by DNA binding to high-affinity spots, suggesting a two-step mechanism for SSB diffusion.</p>
},
	doi = {10.1093/nar/gkx917},
	url = {http://dx.doi.org/10.1093/nar/gkx917},
	author = {Maffeo, Christopher and Aleksei Aksimentiev}
}
