Computational rod theory predicts experimental characteristics of DNA looping by the Lac repressor

Poster Presentation in Biophysical Society Meeting, Baltimore

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There now exist numerous theoretical studies of DNA looping by regulatory proteins using mechanical models. Examples of these models include those developed from nonlinear rod theory and naturally discrete approximations (multi-rigid-body) as well as their combination with MD representations for the protein. Our objective is to demonstrate that such modeling methods lead to quantitative predictions of loop characteristics that are consistent with experimental observations. Herein we employ a computational rod model for DNA. We return to the published experiments of the Kahn group at the University of Maryland and the effects of phasing for DNA sequences with 'designed' bends. A variety of experimental methods including binding competition assays, gel mobility, cyclization, bulk FRET, and SM-FRET provide a wealth of data for comparison with companion numerical experiments resulting from our computational rod model. In particular, we represent the non-planar bent sequences with an intrinsically curved elastic rod that includes two parameters that describe the phasing of the bend relative to the two operators. This model predicts the influence of phasing on, among other things, loop energy, topology (Tw, Wr, Lk), and binding site orientation. These numerical results agree with many experimental observations including: relative loop stabilities, linking number, and binding topology thereby confirming the model's predictive capability. In addition, we exercise the model in directions not previously considered experimentally and reveal new possibilities including specific (designed) sequences that form 'hyper-stable' or 'energetically optimal' loops, which may have intrinsic value in future studies of DNA looping.


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