Free-Energy Calculations for Semi-Flexible Macromolecules: Applications to DNA Knotting and Looping

dc.contributor.ISNI0000 0001 3818 2397 (Levene, SD)
dc.contributor.ResIDG-3100-2010 (Levene, SD)en_US
dc.contributor.authorGiovan, Stefan M.en_US
dc.contributor.authorScharein, Robert G.en_US
dc.contributor.authorHanke, Andreasen_US
dc.contributor.authorLevene, Stephen D.en_US
dc.contributor.utdAuthorGiovan, Stefan M.en_US
dc.contributor.utdAuthorLevene, Stephen D.en_US
dc.date.accessioned2014-11-26T22:29:05Z
dc.date.available2014-11-26T22:29:05Z
dc.date.created2014-11-07en_US
dc.date.issued2014-11-07en_US
dc.description.abstractWe present a method to obtain numerically accurate values of configurational free energies of semiflexible macromolecular systems, based on the technique of thermodynamic integration combined with normal-mode analysis of a reference system subject to harmonic constraints. Compared with previous free-energy calculations that depend on a reference state, our approach introduces two innovations, namely, the use of internal coordinates to constrain the reference states and the ability to freely select these reference states. As a consequence, it is possible to explore systems that undergo substantially larger fluctuations than those considered in previous calculations, including semiflexible biopolymers having arbitrary ratios of contour length L to persistence length P. To validate the method, high accuracy is demonstrated for free energies of prime DNA knots with L/P = 20 and L/P = 40, corresponding to DNA lengths of 3000 and 6000 base pairs, respectively. We then apply the method to study the free-energy landscape for a model of a synaptic nucleoprotein complex containing a pair of looped domains, revealing a bifurcation in the location of optimal synapse (crossover) sites. This transition is relevant to target-site selection by DNA-binding proteins that occupy multiple DNA sites separated by large linear distances along the genome, a problem that arises naturally in gene regulation, DNA recombination, and the action of type-II topoisomerases.;en_US
dc.description.sponsorshipUS National Science Foundation/ (no. DMS-0800929); US National Institutes of Health (no. 2SC3GM083779-04A1)en_US
dc.identifier.bibliographicCitationGiovan, Stefan M., Robert G. Scharein, Andreas Hanke, and Stephen D. Levene. 2014. "Free-energy calculations for semi-flexible macromolecules: Applications to DNA knotting and looping." The Journal of Chemical Physics 141(17): 174902 1-10.en_US
dc.identifier.issn1089-7690en_US
dc.identifier.issue17en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/4228
dc.identifier.volume141en_US
dc.publisherAmerican Institute of Physicsen_US
dc.relation.urihttp://dx.doi.org/10.1063/1.4900657
dc.rightsCC BY 3.0 (Attribution)en_US
dc.rights©2014 The Authorsen_US
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/en_US
dc.sourceThe Journal of Chemical Physics
dc.subjectFree energyen_US
dc.subjectBase pairsen_US
dc.subjectDNAen_US
dc.titleFree-Energy Calculations for Semi-Flexible Macromolecules: Applications to DNA Knotting and Loopingen_US
dc.type.genreArticleen_US

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